diff --git a/Include/internal/pycore_opcode_metadata.h b/Include/internal/pycore_opcode_metadata.h
index 31d2e31573d8c5..618d7538ddef1d 100644
--- a/Include/internal/pycore_opcode_metadata.h
+++ b/Include/internal/pycore_opcode_metadata.h
@@ -1365,11 +1365,11 @@ _PyOpcode_macro_expansion[256] = {
     [BINARY_OP_MULTIPLY_INT] = { .nuops = 5, .uops = { { _GUARD_TOS_INT, OPARG_SIMPLE, 0 }, { _GUARD_NOS_INT, OPARG_SIMPLE, 0 }, { _BINARY_OP_MULTIPLY_INT, OPARG_SIMPLE, 5 }, { _POP_TOP_INT, OPARG_SIMPLE, 5 }, { _POP_TOP_INT, OPARG_SIMPLE, 5 } } },
     [BINARY_OP_SUBSCR_DICT] = { .nuops = 5, .uops = { { _RECORD_NOS_TYPE, OPARG_SIMPLE, 0 }, { _GUARD_NOS_DICT_SUBSCRIPT, OPARG_SIMPLE, 0 }, { _BINARY_OP_SUBSCR_DICT, OPARG_SIMPLE, 5 }, { _POP_TOP, OPARG_SIMPLE, 5 }, { _POP_TOP, OPARG_SIMPLE, 5 } } },
     [BINARY_OP_SUBSCR_GETITEM] = { .nuops = 5, .uops = { { _RECORD_NOS, OPARG_SIMPLE, 0 }, { _CHECK_PEP_523, OPARG_SIMPLE, 5 }, { _BINARY_OP_SUBSCR_CHECK_FUNC, OPARG_SIMPLE, 5 }, { _BINARY_OP_SUBSCR_INIT_CALL, OPARG_SIMPLE, 5 }, { _PUSH_FRAME, OPARG_SIMPLE, 5 } } },
-    [BINARY_OP_SUBSCR_LIST_INT] = { .nuops = 5, .uops = { { _GUARD_TOS_INT, OPARG_SIMPLE, 0 }, { _GUARD_NOS_LIST, OPARG_SIMPLE, 0 }, { _BINARY_OP_SUBSCR_LIST_INT, OPARG_SIMPLE, 5 }, { _POP_TOP_INT, OPARG_SIMPLE, 5 }, { _POP_TOP, OPARG_SIMPLE, 5 } } },
+    [BINARY_OP_SUBSCR_LIST_INT] = { .nuops = 5, .uops = { { _GUARD_TOS_NON_NEGATIVE_COMPACT_INT, OPARG_SIMPLE, 0 }, { _GUARD_NOS_LIST, OPARG_SIMPLE, 0 }, { _BINARY_OP_SUBSCR_LIST_INT, OPARG_SIMPLE, 5 }, { _POP_TOP_INT, OPARG_SIMPLE, 5 }, { _POP_TOP, OPARG_SIMPLE, 5 } } },
     [BINARY_OP_SUBSCR_LIST_SLICE] = { .nuops = 5, .uops = { { _GUARD_TOS_SLICE, OPARG_SIMPLE, 0 }, { _GUARD_NOS_LIST, OPARG_SIMPLE, 0 }, { _BINARY_OP_SUBSCR_LIST_SLICE, OPARG_SIMPLE, 5 }, { _POP_TOP, OPARG_SIMPLE, 5 }, { _POP_TOP, OPARG_SIMPLE, 5 } } },
-    [BINARY_OP_SUBSCR_STR_INT] = { .nuops = 5, .uops = { { _GUARD_TOS_INT, OPARG_SIMPLE, 0 }, { _GUARD_NOS_COMPACT_ASCII, OPARG_SIMPLE, 0 }, { _BINARY_OP_SUBSCR_STR_INT, OPARG_SIMPLE, 5 }, { _POP_TOP_INT, OPARG_SIMPLE, 5 }, { _POP_TOP_UNICODE, OPARG_SIMPLE, 5 } } },
-    [BINARY_OP_SUBSCR_TUPLE_INT] = { .nuops = 6, .uops = { { _GUARD_TOS_INT, OPARG_SIMPLE, 0 }, { _GUARD_NOS_TUPLE, OPARG_SIMPLE, 0 }, { _GUARD_BINARY_OP_SUBSCR_TUPLE_INT_BOUNDS, OPARG_SIMPLE, 0 }, { _BINARY_OP_SUBSCR_TUPLE_INT, OPARG_SIMPLE, 5 }, { _POP_TOP_INT, OPARG_SIMPLE, 5 }, { _POP_TOP, OPARG_SIMPLE, 5 } } },
-    [BINARY_OP_SUBSCR_USTR_INT] = { .nuops = 5, .uops = { { _GUARD_TOS_INT, OPARG_SIMPLE, 0 }, { _GUARD_NOS_UNICODE, OPARG_SIMPLE, 0 }, { _BINARY_OP_SUBSCR_USTR_INT, OPARG_SIMPLE, 5 }, { _POP_TOP_INT, OPARG_SIMPLE, 5 }, { _POP_TOP_UNICODE, OPARG_SIMPLE, 5 } } },
+    [BINARY_OP_SUBSCR_STR_INT] = { .nuops = 5, .uops = { { _GUARD_TOS_NON_NEGATIVE_COMPACT_INT, OPARG_SIMPLE, 0 }, { _GUARD_NOS_COMPACT_ASCII, OPARG_SIMPLE, 0 }, { _BINARY_OP_SUBSCR_STR_INT, OPARG_SIMPLE, 5 }, { _POP_TOP_INT, OPARG_SIMPLE, 5 }, { _POP_TOP_UNICODE, OPARG_SIMPLE, 5 } } },
+    [BINARY_OP_SUBSCR_TUPLE_INT] = { .nuops = 6, .uops = { { _GUARD_TOS_NON_NEGATIVE_COMPACT_INT, OPARG_SIMPLE, 0 }, { _GUARD_NOS_TUPLE, OPARG_SIMPLE, 0 }, { _GUARD_BINARY_OP_SUBSCR_TUPLE_INT_BOUNDS, OPARG_SIMPLE, 0 }, { _BINARY_OP_SUBSCR_TUPLE_INT, OPARG_SIMPLE, 5 }, { _POP_TOP_INT, OPARG_SIMPLE, 5 }, { _POP_TOP, OPARG_SIMPLE, 5 } } },
+    [BINARY_OP_SUBSCR_USTR_INT] = { .nuops = 5, .uops = { { _GUARD_TOS_NON_NEGATIVE_COMPACT_INT, OPARG_SIMPLE, 0 }, { _GUARD_NOS_UNICODE, OPARG_SIMPLE, 0 }, { _BINARY_OP_SUBSCR_USTR_INT, OPARG_SIMPLE, 5 }, { _POP_TOP_INT, OPARG_SIMPLE, 5 }, { _POP_TOP_UNICODE, OPARG_SIMPLE, 5 } } },
     [BINARY_OP_SUBTRACT_FLOAT] = { .nuops = 5, .uops = { { _GUARD_TOS_FLOAT, OPARG_SIMPLE, 0 }, { _GUARD_NOS_FLOAT, OPARG_SIMPLE, 0 }, { _BINARY_OP_SUBTRACT_FLOAT, OPARG_SIMPLE, 5 }, { _POP_TOP_FLOAT, OPARG_SIMPLE, 5 }, { _POP_TOP_FLOAT, OPARG_SIMPLE, 5 } } },
     [BINARY_OP_SUBTRACT_INT] = { .nuops = 5, .uops = { { _GUARD_TOS_INT, OPARG_SIMPLE, 0 }, { _GUARD_NOS_INT, OPARG_SIMPLE, 0 }, { _BINARY_OP_SUBTRACT_INT, OPARG_SIMPLE, 5 }, { _POP_TOP_INT, OPARG_SIMPLE, 5 }, { _POP_TOP_INT, OPARG_SIMPLE, 5 } } },
     [BINARY_SLICE] = { .nuops = 1, .uops = { { _BINARY_SLICE, OPARG_SIMPLE, 0 } } },
@@ -1526,7 +1526,7 @@ _PyOpcode_macro_expansion[256] = {
     [STORE_SLICE] = { .nuops = 1, .uops = { { _STORE_SLICE, OPARG_SIMPLE, 0 } } },
     [STORE_SUBSCR] = { .nuops = 1, .uops = { { _STORE_SUBSCR, OPARG_SIMPLE, 0 } } },
     [STORE_SUBSCR_DICT] = { .nuops = 4, .uops = { { _RECORD_NOS_TYPE, OPARG_SIMPLE, 0 }, { _GUARD_NOS_DICT_STORE_SUBSCRIPT, OPARG_SIMPLE, 0 }, { _STORE_SUBSCR_DICT, OPARG_SIMPLE, 1 }, { _POP_TOP, OPARG_SIMPLE, 1 } } },
-    [STORE_SUBSCR_LIST_INT] = { .nuops = 5, .uops = { { _GUARD_TOS_INT, OPARG_SIMPLE, 0 }, { _GUARD_NOS_LIST, OPARG_SIMPLE, 0 }, { _STORE_SUBSCR_LIST_INT, OPARG_SIMPLE, 1 }, { _POP_TOP_INT, OPARG_SIMPLE, 1 }, { _POP_TOP, OPARG_SIMPLE, 1 } } },
+    [STORE_SUBSCR_LIST_INT] = { .nuops = 5, .uops = { { _GUARD_TOS_NON_NEGATIVE_COMPACT_INT, OPARG_SIMPLE, 0 }, { _GUARD_NOS_LIST, OPARG_SIMPLE, 0 }, { _STORE_SUBSCR_LIST_INT, OPARG_SIMPLE, 1 }, { _POP_TOP_INT, OPARG_SIMPLE, 1 }, { _POP_TOP, OPARG_SIMPLE, 1 } } },
     [SWAP] = { .nuops = 1, .uops = { { _SWAP, OPARG_SIMPLE, 0 } } },
     [TO_BOOL] = { .nuops = 1, .uops = { { _TO_BOOL, OPARG_SIMPLE, 2 } } },
     [TO_BOOL_ALWAYS_TRUE] = { .nuops = 4, .uops = { { _RECORD_TOS_TYPE, OPARG_SIMPLE, 1 }, { _GUARD_TYPE_VERSION, 2, 1 }, { _REPLACE_WITH_TRUE, OPARG_SIMPLE, 3 }, { _POP_TOP, OPARG_SIMPLE, 3 } } },
diff --git a/Include/internal/pycore_uop_ids.h b/Include/internal/pycore_uop_ids.h
index 97f934727a85a3..5f66c2a6868d3b 100644
--- a/Include/internal/pycore_uop_ids.h
+++ b/Include/internal/pycore_uop_ids.h
@@ -199,6 +199,7 @@ enum {
     _GUARD_TOS_INT,
     _GUARD_TOS_IS_NONE,
     _GUARD_TOS_LIST,
+    _GUARD_TOS_NON_NEGATIVE_COMPACT_INT,
     _GUARD_TOS_NOT_NULL,
     _GUARD_TOS_OVERFLOWED,
     _GUARD_TOS_SET,
@@ -364,7 +365,7 @@ enum {
     _UNPACK_SEQUENCE_UNIQUE_TWO_TUPLE,
     _YIELD_VALUE,
 };
-#define MAX_UOP_ID 652
+#define MAX_UOP_ID 653
 
 #define _BUILD_INTERPOLATION BUILD_INTERPOLATION
 #define _BUILD_LIST BUILD_LIST
@@ -950,6 +951,10 @@ enum {
     _GUARD_TOS_LIST_r11,
     _GUARD_TOS_LIST_r22,
     _GUARD_TOS_LIST_r33,
+    _GUARD_TOS_NON_NEGATIVE_COMPACT_INT_r01,
+    _GUARD_TOS_NON_NEGATIVE_COMPACT_INT_r11,
+    _GUARD_TOS_NON_NEGATIVE_COMPACT_INT_r22,
+    _GUARD_TOS_NON_NEGATIVE_COMPACT_INT_r33,
     _GUARD_TOS_NOT_NULL_r01,
     _GUARD_TOS_NOT_NULL_r11,
     _GUARD_TOS_NOT_NULL_r22,
@@ -1434,7 +1439,7 @@ enum {
     _WITH_EXCEPT_START_r33,
     _YIELD_VALUE_r11,
 };
-#define MAX_UOP_REGS_ID 1645
+#define MAX_UOP_REGS_ID 1650
 
 #ifdef __cplusplus
 }
diff --git a/Include/internal/pycore_uop_metadata.h b/Include/internal/pycore_uop_metadata.h
index 990706c0b32922..2c594c620d3651 100644
--- a/Include/internal/pycore_uop_metadata.h
+++ b/Include/internal/pycore_uop_metadata.h
@@ -156,6 +156,7 @@ const uint32_t _PyUop_Flags[MAX_UOP_ID+1] = {
     [_LIST_APPEND] = HAS_ARG_FLAG | HAS_ERROR_FLAG,
     [_SET_ADD] = HAS_ARG_FLAG | HAS_ERROR_FLAG | HAS_ESCAPES_FLAG,
     [_STORE_SUBSCR] = HAS_ERROR_FLAG | HAS_ESCAPES_FLAG,
+    [_GUARD_TOS_NON_NEGATIVE_COMPACT_INT] = HAS_EXIT_FLAG,
     [_STORE_SUBSCR_LIST_INT] = HAS_DEOPT_FLAG | HAS_ESCAPES_FLAG,
     [_STORE_SUBSCR_DICT] = HAS_ERROR_FLAG | HAS_ESCAPES_FLAG,
     [_STORE_SUBSCR_DICT_KNOWN_HASH] = HAS_ERROR_FLAG | HAS_ESCAPES_FLAG,
@@ -1533,6 +1534,15 @@ const _PyUopCachingInfo _PyUop_Caching[MAX_UOP_ID+1] = {
             { 0, 3, _STORE_SUBSCR_r30 },
         },
     },
+    [_GUARD_TOS_NON_NEGATIVE_COMPACT_INT] = {
+        .best = { 0, 1, 2, 3 },
+        .entries = {
+            { 1, 0, _GUARD_TOS_NON_NEGATIVE_COMPACT_INT_r01 },
+            { 1, 1, _GUARD_TOS_NON_NEGATIVE_COMPACT_INT_r11 },
+            { 2, 2, _GUARD_TOS_NON_NEGATIVE_COMPACT_INT_r22 },
+            { 3, 3, _GUARD_TOS_NON_NEGATIVE_COMPACT_INT_r33 },
+        },
+    },
     [_STORE_SUBSCR_LIST_INT] = {
         .best = { 3, 3, 3, 3 },
         .entries = {
@@ -4237,6 +4247,10 @@ const uint16_t _PyUop_Uncached[MAX_UOP_REGS_ID+1] = {
     [_LIST_APPEND_r10] = _LIST_APPEND,
     [_SET_ADD_r10] = _SET_ADD,
     [_STORE_SUBSCR_r30] = _STORE_SUBSCR,
+    [_GUARD_TOS_NON_NEGATIVE_COMPACT_INT_r01] = _GUARD_TOS_NON_NEGATIVE_COMPACT_INT,
+    [_GUARD_TOS_NON_NEGATIVE_COMPACT_INT_r11] = _GUARD_TOS_NON_NEGATIVE_COMPACT_INT,
+    [_GUARD_TOS_NON_NEGATIVE_COMPACT_INT_r22] = _GUARD_TOS_NON_NEGATIVE_COMPACT_INT,
+    [_GUARD_TOS_NON_NEGATIVE_COMPACT_INT_r33] = _GUARD_TOS_NON_NEGATIVE_COMPACT_INT,
     [_STORE_SUBSCR_LIST_INT_r32] = _STORE_SUBSCR_LIST_INT,
     [_STORE_SUBSCR_DICT_r31] = _STORE_SUBSCR_DICT,
     [_STORE_SUBSCR_DICT_KNOWN_HASH_r31] = _STORE_SUBSCR_DICT_KNOWN_HASH,
@@ -5536,6 +5550,11 @@ const char *const _PyOpcode_uop_name[MAX_UOP_REGS_ID+1] = {
     [_GUARD_TOS_LIST_r11] = "_GUARD_TOS_LIST_r11",
     [_GUARD_TOS_LIST_r22] = "_GUARD_TOS_LIST_r22",
     [_GUARD_TOS_LIST_r33] = "_GUARD_TOS_LIST_r33",
+    [_GUARD_TOS_NON_NEGATIVE_COMPACT_INT] = "_GUARD_TOS_NON_NEGATIVE_COMPACT_INT",
+    [_GUARD_TOS_NON_NEGATIVE_COMPACT_INT_r01] = "_GUARD_TOS_NON_NEGATIVE_COMPACT_INT_r01",
+    [_GUARD_TOS_NON_NEGATIVE_COMPACT_INT_r11] = "_GUARD_TOS_NON_NEGATIVE_COMPACT_INT_r11",
+    [_GUARD_TOS_NON_NEGATIVE_COMPACT_INT_r22] = "_GUARD_TOS_NON_NEGATIVE_COMPACT_INT_r22",
+    [_GUARD_TOS_NON_NEGATIVE_COMPACT_INT_r33] = "_GUARD_TOS_NON_NEGATIVE_COMPACT_INT_r33",
     [_GUARD_TOS_NOT_NULL] = "_GUARD_TOS_NOT_NULL",
     [_GUARD_TOS_NOT_NULL_r01] = "_GUARD_TOS_NOT_NULL_r01",
     [_GUARD_TOS_NOT_NULL_r11] = "_GUARD_TOS_NOT_NULL_r11",
@@ -6389,6 +6408,8 @@ int _PyUop_num_popped(int opcode, int oparg)
             return 1;
         case _STORE_SUBSCR:
             return 3;
+        case _GUARD_TOS_NON_NEGATIVE_COMPACT_INT:
+            return 0;
         case _STORE_SUBSCR_LIST_INT:
             return 3;
         case _STORE_SUBSCR_DICT:
diff --git a/Misc/NEWS.d/next/Core_and_Builtins/2026-07-10-10-05-00.gh-issue-153486.compact-index-guard.rst b/Misc/NEWS.d/next/Core_and_Builtins/2026-07-10-10-05-00.gh-issue-153486.compact-index-guard.rst
new file mode 100644
index 00000000000000..524461453885e9
--- /dev/null
+++ b/Misc/NEWS.d/next/Core_and_Builtins/2026-07-10-10-05-00.gh-issue-153486.compact-index-guard.rst
@@ -0,0 +1,2 @@
+Improve optimized handling of non-negative integer indices for lists,
+tuples, and strings.
diff --git a/Modules/_testinternalcapi/test_cases.c.h b/Modules/_testinternalcapi/test_cases.c.h
index a17648a33d4fe4..ff30c2aa6ddadd 100644
--- a/Modules/_testinternalcapi/test_cases.c.h
+++ b/Modules/_testinternalcapi/test_cases.c.h
@@ -823,11 +823,16 @@
             _PyStackRef res;
             _PyStackRef ls;
             _PyStackRef ss;
-            // _GUARD_TOS_INT
+            // _GUARD_TOS_NON_NEGATIVE_COMPACT_INT
             {
                 value = stack_pointer[-1];
                 PyObject *value_o = PyStackRef_AsPyObjectBorrow(value);
-                if (!_PyLong_CheckExactAndCompact(value_o)) {
+                if (!PyLong_CheckExact(value_o)) {
+                    UPDATE_MISS_STATS(BINARY_OP);
+                    assert(_PyOpcode_Deopt[opcode] == (BINARY_OP));
+                    JUMP_TO_PREDICTED(BINARY_OP);
+                }
+                if (!_PyLong_IsNonNegativeCompact((PyLongObject *)value_o)) {
                     UPDATE_MISS_STATS(BINARY_OP);
                     assert(_PyOpcode_Deopt[opcode] == (BINARY_OP));
                     JUMP_TO_PREDICTED(BINARY_OP);
@@ -853,9 +858,6 @@
                 assert(PyLong_CheckExact(sub));
                 assert(PyList_CheckExact(list));
                 Py_ssize_t index = _PyLong_CompactValue((PyLongObject *)sub);
-                if (index < 0) {
-                    index += PyList_GET_SIZE(list);
-                }
                 #ifdef Py_GIL_DISABLED
                 _PyFrame_SetStackPointer(frame, stack_pointer);
                 _PyFrame_StackPointerValidate(frame);
@@ -1002,11 +1004,16 @@
             _PyStackRef res;
             _PyStackRef s;
             _PyStackRef i;
-            // _GUARD_TOS_INT
+            // _GUARD_TOS_NON_NEGATIVE_COMPACT_INT
             {
                 value = stack_pointer[-1];
                 PyObject *value_o = PyStackRef_AsPyObjectBorrow(value);
-                if (!_PyLong_CheckExactAndCompact(value_o)) {
+                if (!PyLong_CheckExact(value_o)) {
+                    UPDATE_MISS_STATS(BINARY_OP);
+                    assert(_PyOpcode_Deopt[opcode] == (BINARY_OP));
+                    JUMP_TO_PREDICTED(BINARY_OP);
+                }
+                if (!_PyLong_IsNonNegativeCompact((PyLongObject *)value_o)) {
                     UPDATE_MISS_STATS(BINARY_OP);
                     assert(_PyOpcode_Deopt[opcode] == (BINARY_OP));
                     JUMP_TO_PREDICTED(BINARY_OP);
@@ -1036,11 +1043,6 @@
                 PyObject *str = PyStackRef_AsPyObjectBorrow(str_st);
                 assert(PyLong_CheckExact(sub));
                 assert(PyUnicode_CheckExact(str));
-                if (!_PyLong_IsNonNegativeCompact((PyLongObject*)sub)) {
-                    UPDATE_MISS_STATS(BINARY_OP);
-                    assert(_PyOpcode_Deopt[opcode] == (BINARY_OP));
-                    JUMP_TO_PREDICTED(BINARY_OP);
-                }
                 Py_ssize_t index = ((PyLongObject*)sub)->long_value.ob_digit[0];
                 if (PyUnicode_GET_LENGTH(str) <= index) {
                     UPDATE_MISS_STATS(BINARY_OP);
@@ -1091,11 +1093,16 @@
             _PyStackRef res;
             _PyStackRef ts;
             _PyStackRef ss;
-            // _GUARD_TOS_INT
+            // _GUARD_TOS_NON_NEGATIVE_COMPACT_INT
             {
                 value = stack_pointer[-1];
                 PyObject *value_o = PyStackRef_AsPyObjectBorrow(value);
-                if (!_PyLong_CheckExactAndCompact(value_o)) {
+                if (!PyLong_CheckExact(value_o)) {
+                    UPDATE_MISS_STATS(BINARY_OP);
+                    assert(_PyOpcode_Deopt[opcode] == (BINARY_OP));
+                    JUMP_TO_PREDICTED(BINARY_OP);
+                }
+                if (!_PyLong_IsNonNegativeCompact((PyLongObject *)value_o)) {
                     UPDATE_MISS_STATS(BINARY_OP);
                     assert(_PyOpcode_Deopt[opcode] == (BINARY_OP));
                     JUMP_TO_PREDICTED(BINARY_OP);
@@ -1119,11 +1126,6 @@
                 PyObject *tuple = PyStackRef_AsPyObjectBorrow(tuple_st);
                 assert(PyLong_CheckExact(sub));
                 assert(PyTuple_CheckExact(tuple));
-                if (!_PyLong_IsNonNegativeCompact((PyLongObject *)sub)) {
-                    UPDATE_MISS_STATS(BINARY_OP);
-                    assert(_PyOpcode_Deopt[opcode] == (BINARY_OP));
-                    JUMP_TO_PREDICTED(BINARY_OP);
-                }
                 Py_ssize_t index = ((PyLongObject*)sub)->long_value.ob_digit[0];
                 if (index >= PyTuple_GET_SIZE(tuple)) {
                     UPDATE_MISS_STATS(BINARY_OP);
@@ -1184,11 +1186,16 @@
             _PyStackRef res;
             _PyStackRef s;
             _PyStackRef i;
-            // _GUARD_TOS_INT
+            // _GUARD_TOS_NON_NEGATIVE_COMPACT_INT
             {
                 value = stack_pointer[-1];
                 PyObject *value_o = PyStackRef_AsPyObjectBorrow(value);
-                if (!_PyLong_CheckExactAndCompact(value_o)) {
+                if (!PyLong_CheckExact(value_o)) {
+                    UPDATE_MISS_STATS(BINARY_OP);
+                    assert(_PyOpcode_Deopt[opcode] == (BINARY_OP));
+                    JUMP_TO_PREDICTED(BINARY_OP);
+                }
+                if (!_PyLong_IsNonNegativeCompact((PyLongObject *)value_o)) {
                     UPDATE_MISS_STATS(BINARY_OP);
                     assert(_PyOpcode_Deopt[opcode] == (BINARY_OP));
                     JUMP_TO_PREDICTED(BINARY_OP);
@@ -1213,11 +1220,6 @@
                 PyObject *str = PyStackRef_AsPyObjectBorrow(str_st);
                 assert(PyLong_CheckExact(sub));
                 assert(PyUnicode_CheckExact(str));
-                if (!_PyLong_IsNonNegativeCompact((PyLongObject*)sub)) {
-                    UPDATE_MISS_STATS(BINARY_OP);
-                    assert(_PyOpcode_Deopt[opcode] == (BINARY_OP));
-                    JUMP_TO_PREDICTED(BINARY_OP);
-                }
                 Py_ssize_t index = ((PyLongObject*)sub)->long_value.ob_digit[0];
                 if (PyUnicode_GET_LENGTH(str) <= index) {
                     UPDATE_MISS_STATS(BINARY_OP);
@@ -12753,11 +12755,16 @@
             _PyStackRef sub_st;
             _PyStackRef ls;
             _PyStackRef ss;
-            // _GUARD_TOS_INT
+            // _GUARD_TOS_NON_NEGATIVE_COMPACT_INT
             {
                 value = stack_pointer[-1];
                 PyObject *value_o = PyStackRef_AsPyObjectBorrow(value);
-                if (!_PyLong_CheckExactAndCompact(value_o)) {
+                if (!PyLong_CheckExact(value_o)) {
+                    UPDATE_MISS_STATS(STORE_SUBSCR);
+                    assert(_PyOpcode_Deopt[opcode] == (STORE_SUBSCR));
+                    JUMP_TO_PREDICTED(STORE_SUBSCR);
+                }
+                if (!_PyLong_IsNonNegativeCompact((PyLongObject *)value_o)) {
                     UPDATE_MISS_STATS(STORE_SUBSCR);
                     assert(_PyOpcode_Deopt[opcode] == (STORE_SUBSCR));
                     JUMP_TO_PREDICTED(STORE_SUBSCR);
@@ -12790,10 +12797,7 @@
                     JUMP_TO_PREDICTED(STORE_SUBSCR);
                 }
                 Py_ssize_t len = PyList_GET_SIZE(list);
-                if (index < 0) {
-                    index += len;
-                }
-                if (index < 0 || index >= len) {
+                if (index >= len) {
                     UNLOCK_OBJECT(list);
                     if (true) {
                         UPDATE_MISS_STATS(STORE_SUBSCR);
diff --git a/Python/bytecodes.c b/Python/bytecodes.c
index 4d7b338e2dbd4c..cba6b7c3704587 100644
--- a/Python/bytecodes.c
+++ b/Python/bytecodes.c
@@ -1134,7 +1134,8 @@ dummy_func(
         macro(STORE_SLICE) = _SPECIALIZE_STORE_SLICE + _STORE_SLICE;
 
         macro(BINARY_OP_SUBSCR_LIST_INT) =
-            _GUARD_TOS_INT + _GUARD_NOS_LIST + unused/5 + _BINARY_OP_SUBSCR_LIST_INT + _POP_TOP_INT + POP_TOP;
+            _GUARD_TOS_NON_NEGATIVE_COMPACT_INT + _GUARD_NOS_LIST +
+            unused/5 + _BINARY_OP_SUBSCR_LIST_INT + _POP_TOP_INT + POP_TOP;
 
         op(_BINARY_OP_SUBSCR_LIST_INT, (list_st, sub_st -- res, ls, ss)) {
             PyObject *sub = PyStackRef_AsPyObjectBorrow(sub_st);
@@ -1144,9 +1145,6 @@ dummy_func(
             assert(PyList_CheckExact(list));
 
             Py_ssize_t index = _PyLong_CompactValue((PyLongObject *)sub);
-            if (index < 0) {
-                index += PyList_GET_SIZE(list);
-            }
 #ifdef Py_GIL_DISABLED
             PyObject *res_o = _PyList_GetItemRef((PyListObject*)list, index);
             EXIT_IF(res_o == NULL);
@@ -1185,7 +1183,8 @@ dummy_func(
         }
 
         macro(BINARY_OP_SUBSCR_STR_INT) =
-            _GUARD_TOS_INT + _GUARD_NOS_COMPACT_ASCII + unused/5 + _BINARY_OP_SUBSCR_STR_INT + _POP_TOP_INT + _POP_TOP_UNICODE;
+            _GUARD_TOS_NON_NEGATIVE_COMPACT_INT + _GUARD_NOS_COMPACT_ASCII +
+            unused/5 + _BINARY_OP_SUBSCR_STR_INT + _POP_TOP_INT + _POP_TOP_UNICODE;
 
         op(_BINARY_OP_SUBSCR_STR_INT, (str_st, sub_st -- res, s, i)) {
             PyObject *sub = PyStackRef_AsPyObjectBorrow(sub_st);
@@ -1193,7 +1192,6 @@ dummy_func(
 
             assert(PyLong_CheckExact(sub));
             assert(PyUnicode_CheckExact(str));
-            EXIT_IF(!_PyLong_IsNonNegativeCompact((PyLongObject*)sub));
             Py_ssize_t index = ((PyLongObject*)sub)->long_value.ob_digit[0];
             EXIT_IF(PyUnicode_GET_LENGTH(str) <= index);
             uint8_t c = PyUnicode_1BYTE_DATA(str)[index];
@@ -1207,7 +1205,8 @@ dummy_func(
         }
 
         macro(BINARY_OP_SUBSCR_USTR_INT) =
-            _GUARD_TOS_INT + _GUARD_NOS_UNICODE + unused/5 + _BINARY_OP_SUBSCR_USTR_INT + _POP_TOP_INT + _POP_TOP_UNICODE;
+            _GUARD_TOS_NON_NEGATIVE_COMPACT_INT + _GUARD_NOS_UNICODE +
+            unused/5 + _BINARY_OP_SUBSCR_USTR_INT + _POP_TOP_INT + _POP_TOP_UNICODE;
 
         op(_BINARY_OP_SUBSCR_USTR_INT, (str_st, sub_st -- res, s, i)) {
             PyObject *sub = PyStackRef_AsPyObjectBorrow(sub_st);
@@ -1215,7 +1214,6 @@ dummy_func(
 
             assert(PyLong_CheckExact(sub));
             assert(PyUnicode_CheckExact(str));
-            EXIT_IF(!_PyLong_IsNonNegativeCompact((PyLongObject*)sub));
             Py_ssize_t index = ((PyLongObject*)sub)->long_value.ob_digit[0];
             EXIT_IF(PyUnicode_GET_LENGTH(str) <= index);
             // Specialize for reading an ASCII character from any string:
@@ -1240,7 +1238,7 @@ dummy_func(
         }
 
         macro(BINARY_OP_SUBSCR_TUPLE_INT) =
-            _GUARD_TOS_INT +
+            _GUARD_TOS_NON_NEGATIVE_COMPACT_INT +
             _GUARD_NOS_TUPLE +
             _GUARD_BINARY_OP_SUBSCR_TUPLE_INT_BOUNDS +
             unused/5 +
@@ -1256,8 +1254,7 @@ dummy_func(
             assert(PyLong_CheckExact(sub));
             assert(PyTuple_CheckExact(tuple));
 
-            // Deopt unless 0 <= sub < PyTuple_Size(list)
-            EXIT_IF(!_PyLong_IsNonNegativeCompact((PyLongObject *)sub));
+            // Deopt unless sub < PyTuple_Size(list)
             Py_ssize_t index = ((PyLongObject*)sub)->long_value.ob_digit[0];
             EXIT_IF(index >= PyTuple_GET_SIZE(tuple));
         }
@@ -1411,8 +1408,15 @@ dummy_func(
 
         macro(STORE_SUBSCR) = _SPECIALIZE_STORE_SUBSCR + _STORE_SUBSCR;
 
+        op(_GUARD_TOS_NON_NEGATIVE_COMPACT_INT, (value -- value)) {
+            PyObject *value_o = PyStackRef_AsPyObjectBorrow(value);
+            EXIT_IF(!PyLong_CheckExact(value_o));
+            EXIT_IF(!_PyLong_IsNonNegativeCompact((PyLongObject *)value_o));
+        }
+
         macro(STORE_SUBSCR_LIST_INT) =
-            _GUARD_TOS_INT + _GUARD_NOS_LIST + unused/1 + _STORE_SUBSCR_LIST_INT + _POP_TOP_INT + POP_TOP;
+            _GUARD_TOS_NON_NEGATIVE_COMPACT_INT + _GUARD_NOS_LIST +
+            unused/1 + _STORE_SUBSCR_LIST_INT + _POP_TOP_INT + POP_TOP;
 
         op(_STORE_SUBSCR_LIST_INT, (value, list_st, sub_st -- ls, ss)) {
             PyObject *sub = PyStackRef_AsPyObjectBorrow(sub_st);
@@ -1424,11 +1428,7 @@ dummy_func(
             Py_ssize_t index = _PyLong_CompactValue((PyLongObject *)sub);
             DEOPT_IF(!LOCK_OBJECT(list));
             Py_ssize_t len = PyList_GET_SIZE(list);
-            // Ensure index < len(list)
-            if (index < 0) {
-                index += len;
-            }
-            if (index < 0 || index >= len) {
+            if (index >= len) {
                 UNLOCK_OBJECT(list);
                 DEOPT_IF(true);
             }
diff --git a/Python/executor_cases.c.h b/Python/executor_cases.c.h
index e45bbd7cceb295..4afeda706efe28 100644
--- a/Python/executor_cases.c.h
+++ b/Python/executor_cases.c.h
@@ -6912,9 +6912,6 @@
             assert(PyLong_CheckExact(sub));
             assert(PyList_CheckExact(list));
             Py_ssize_t index = _PyLong_CompactValue((PyLongObject *)sub);
-            if (index < 0) {
-                index += PyList_GET_SIZE(list);
-            }
             #ifdef Py_GIL_DISABLED
             stack_pointer[0] = list_st;
             stack_pointer[1] = sub_st;
@@ -7018,13 +7015,6 @@
             PyObject *str = PyStackRef_AsPyObjectBorrow(str_st);
             assert(PyLong_CheckExact(sub));
             assert(PyUnicode_CheckExact(str));
-            if (!_PyLong_IsNonNegativeCompact((PyLongObject*)sub)) {
-                UOP_STAT_INC(uopcode, miss);
-                _tos_cache1 = sub_st;
-                _tos_cache0 = str_st;
-                SET_CURRENT_CACHED_VALUES(2);
-                JUMP_TO_JUMP_TARGET();
-            }
             Py_ssize_t index = ((PyLongObject*)sub)->long_value.ob_digit[0];
             if (PyUnicode_GET_LENGTH(str) <= index) {
                 UOP_STAT_INC(uopcode, miss);
@@ -7064,13 +7054,6 @@
             PyObject *str = PyStackRef_AsPyObjectBorrow(str_st);
             assert(PyLong_CheckExact(sub));
             assert(PyUnicode_CheckExact(str));
-            if (!_PyLong_IsNonNegativeCompact((PyLongObject*)sub)) {
-                UOP_STAT_INC(uopcode, miss);
-                _tos_cache1 = sub_st;
-                _tos_cache0 = str_st;
-                SET_CURRENT_CACHED_VALUES(2);
-                JUMP_TO_JUMP_TARGET();
-            }
             Py_ssize_t index = ((PyLongObject*)sub)->long_value.ob_digit[0];
             if (PyUnicode_GET_LENGTH(str) <= index) {
                 UOP_STAT_INC(uopcode, miss);
@@ -7285,11 +7268,6 @@
             PyObject *tuple = PyStackRef_AsPyObjectBorrow(tuple_st);
             assert(PyLong_CheckExact(sub));
             assert(PyTuple_CheckExact(tuple));
-            if (!_PyLong_IsNonNegativeCompact((PyLongObject *)sub)) {
-                UOP_STAT_INC(uopcode, miss);
-                SET_CURRENT_CACHED_VALUES(0);
-                JUMP_TO_JUMP_TARGET();
-            }
             Py_ssize_t index = ((PyLongObject*)sub)->long_value.ob_digit[0];
             if (index >= PyTuple_GET_SIZE(tuple)) {
                 UOP_STAT_INC(uopcode, miss);
@@ -7317,12 +7295,6 @@
             PyObject *tuple = PyStackRef_AsPyObjectBorrow(tuple_st);
             assert(PyLong_CheckExact(sub));
             assert(PyTuple_CheckExact(tuple));
-            if (!_PyLong_IsNonNegativeCompact((PyLongObject *)sub)) {
-                UOP_STAT_INC(uopcode, miss);
-                _tos_cache0 = sub_st;
-                SET_CURRENT_CACHED_VALUES(1);
-                JUMP_TO_JUMP_TARGET();
-            }
             Py_ssize_t index = ((PyLongObject*)sub)->long_value.ob_digit[0];
             if (index >= PyTuple_GET_SIZE(tuple)) {
                 UOP_STAT_INC(uopcode, miss);
@@ -7352,13 +7324,6 @@
             PyObject *tuple = PyStackRef_AsPyObjectBorrow(tuple_st);
             assert(PyLong_CheckExact(sub));
             assert(PyTuple_CheckExact(tuple));
-            if (!_PyLong_IsNonNegativeCompact((PyLongObject *)sub)) {
-                UOP_STAT_INC(uopcode, miss);
-                _tos_cache1 = sub_st;
-                _tos_cache0 = tuple_st;
-                SET_CURRENT_CACHED_VALUES(2);
-                JUMP_TO_JUMP_TARGET();
-            }
             Py_ssize_t index = ((PyLongObject*)sub)->long_value.ob_digit[0];
             if (index >= PyTuple_GET_SIZE(tuple)) {
                 UOP_STAT_INC(uopcode, miss);
@@ -7388,14 +7353,6 @@
             PyObject *tuple = PyStackRef_AsPyObjectBorrow(tuple_st);
             assert(PyLong_CheckExact(sub));
             assert(PyTuple_CheckExact(tuple));
-            if (!_PyLong_IsNonNegativeCompact((PyLongObject *)sub)) {
-                UOP_STAT_INC(uopcode, miss);
-                _tos_cache2 = sub_st;
-                _tos_cache1 = tuple_st;
-                _tos_cache0 = _stack_item_0;
-                SET_CURRENT_CACHED_VALUES(3);
-                JUMP_TO_JUMP_TARGET();
-            }
             Py_ssize_t index = ((PyLongObject*)sub)->long_value.ob_digit[0];
             if (index >= PyTuple_GET_SIZE(tuple)) {
                 UOP_STAT_INC(uopcode, miss);
@@ -8341,6 +8298,117 @@
             break;
         }
 
+        case _GUARD_TOS_NON_NEGATIVE_COMPACT_INT_r01: {
+            CHECK_CURRENT_CACHED_VALUES(0);
+            ASSERT_WITHIN_STACK_BOUNDS_IGNORING_CACHE(__FILE__, __LINE__);
+            _PyStackRef value;
+            value = stack_pointer[-1];
+            PyObject *value_o = PyStackRef_AsPyObjectBorrow(value);
+            if (!PyLong_CheckExact(value_o)) {
+                UOP_STAT_INC(uopcode, miss);
+                SET_CURRENT_CACHED_VALUES(0);
+                JUMP_TO_JUMP_TARGET();
+            }
+            if (!_PyLong_IsNonNegativeCompact((PyLongObject *)value_o)) {
+                UOP_STAT_INC(uopcode, miss);
+                SET_CURRENT_CACHED_VALUES(0);
+                JUMP_TO_JUMP_TARGET();
+            }
+            _tos_cache0 = value;
+            SET_CURRENT_CACHED_VALUES(1);
+            stack_pointer += -1;
+            ASSERT_WITHIN_STACK_BOUNDS(__FILE__, __LINE__);
+            ASSERT_WITHIN_STACK_BOUNDS_IGNORING_CACHE(__FILE__, __LINE__);
+            break;
+        }
+
+        case _GUARD_TOS_NON_NEGATIVE_COMPACT_INT_r11: {
+            CHECK_CURRENT_CACHED_VALUES(1);
+            ASSERT_WITHIN_STACK_BOUNDS_IGNORING_CACHE(__FILE__, __LINE__);
+            _PyStackRef value;
+            _PyStackRef _stack_item_0 = _tos_cache0;
+            value = _stack_item_0;
+            PyObject *value_o = PyStackRef_AsPyObjectBorrow(value);
+            if (!PyLong_CheckExact(value_o)) {
+                UOP_STAT_INC(uopcode, miss);
+                _tos_cache0 = value;
+                SET_CURRENT_CACHED_VALUES(1);
+                JUMP_TO_JUMP_TARGET();
+            }
+            if (!_PyLong_IsNonNegativeCompact((PyLongObject *)value_o)) {
+                UOP_STAT_INC(uopcode, miss);
+                _tos_cache0 = value;
+                SET_CURRENT_CACHED_VALUES(1);
+                JUMP_TO_JUMP_TARGET();
+            }
+            _tos_cache0 = value;
+            SET_CURRENT_CACHED_VALUES(1);
+            ASSERT_WITHIN_STACK_BOUNDS_IGNORING_CACHE(__FILE__, __LINE__);
+            break;
+        }
+
+        case _GUARD_TOS_NON_NEGATIVE_COMPACT_INT_r22: {
+            CHECK_CURRENT_CACHED_VALUES(2);
+            ASSERT_WITHIN_STACK_BOUNDS_IGNORING_CACHE(__FILE__, __LINE__);
+            _PyStackRef value;
+            _PyStackRef _stack_item_0 = _tos_cache0;
+            _PyStackRef _stack_item_1 = _tos_cache1;
+            value = _stack_item_1;
+            PyObject *value_o = PyStackRef_AsPyObjectBorrow(value);
+            if (!PyLong_CheckExact(value_o)) {
+                UOP_STAT_INC(uopcode, miss);
+                _tos_cache1 = value;
+                _tos_cache0 = _stack_item_0;
+                SET_CURRENT_CACHED_VALUES(2);
+                JUMP_TO_JUMP_TARGET();
+            }
+            if (!_PyLong_IsNonNegativeCompact((PyLongObject *)value_o)) {
+                UOP_STAT_INC(uopcode, miss);
+                _tos_cache1 = value;
+                _tos_cache0 = _stack_item_0;
+                SET_CURRENT_CACHED_VALUES(2);
+                JUMP_TO_JUMP_TARGET();
+            }
+            _tos_cache1 = value;
+            _tos_cache0 = _stack_item_0;
+            SET_CURRENT_CACHED_VALUES(2);
+            ASSERT_WITHIN_STACK_BOUNDS_IGNORING_CACHE(__FILE__, __LINE__);
+            break;
+        }
+
+        case _GUARD_TOS_NON_NEGATIVE_COMPACT_INT_r33: {
+            CHECK_CURRENT_CACHED_VALUES(3);
+            ASSERT_WITHIN_STACK_BOUNDS_IGNORING_CACHE(__FILE__, __LINE__);
+            _PyStackRef value;
+            _PyStackRef _stack_item_0 = _tos_cache0;
+            _PyStackRef _stack_item_1 = _tos_cache1;
+            _PyStackRef _stack_item_2 = _tos_cache2;
+            value = _stack_item_2;
+            PyObject *value_o = PyStackRef_AsPyObjectBorrow(value);
+            if (!PyLong_CheckExact(value_o)) {
+                UOP_STAT_INC(uopcode, miss);
+                _tos_cache2 = value;
+                _tos_cache1 = _stack_item_1;
+                _tos_cache0 = _stack_item_0;
+                SET_CURRENT_CACHED_VALUES(3);
+                JUMP_TO_JUMP_TARGET();
+            }
+            if (!_PyLong_IsNonNegativeCompact((PyLongObject *)value_o)) {
+                UOP_STAT_INC(uopcode, miss);
+                _tos_cache2 = value;
+                _tos_cache1 = _stack_item_1;
+                _tos_cache0 = _stack_item_0;
+                SET_CURRENT_CACHED_VALUES(3);
+                JUMP_TO_JUMP_TARGET();
+            }
+            _tos_cache2 = value;
+            _tos_cache1 = _stack_item_1;
+            _tos_cache0 = _stack_item_0;
+            SET_CURRENT_CACHED_VALUES(3);
+            ASSERT_WITHIN_STACK_BOUNDS_IGNORING_CACHE(__FILE__, __LINE__);
+            break;
+        }
+
         case _STORE_SUBSCR_LIST_INT_r32: {
             CHECK_CURRENT_CACHED_VALUES(3);
             ASSERT_WITHIN_STACK_BOUNDS_IGNORING_CACHE(__FILE__, __LINE__);
@@ -8369,10 +8437,7 @@
                 JUMP_TO_JUMP_TARGET();
             }
             Py_ssize_t len = PyList_GET_SIZE(list);
-            if (index < 0) {
-                index += len;
-            }
-            if (index < 0 || index >= len) {
+            if (index >= len) {
                 UNLOCK_OBJECT(list);
                 if (true) {
                     UOP_STAT_INC(uopcode, miss);
diff --git a/Python/generated_cases.c.h b/Python/generated_cases.c.h
index 6178dc70c1b80e..f670f622b33304 100644
--- a/Python/generated_cases.c.h
+++ b/Python/generated_cases.c.h
@@ -823,11 +823,16 @@
             _PyStackRef res;
             _PyStackRef ls;
             _PyStackRef ss;
-            // _GUARD_TOS_INT
+            // _GUARD_TOS_NON_NEGATIVE_COMPACT_INT
             {
                 value = stack_pointer[-1];
                 PyObject *value_o = PyStackRef_AsPyObjectBorrow(value);
-                if (!_PyLong_CheckExactAndCompact(value_o)) {
+                if (!PyLong_CheckExact(value_o)) {
+                    UPDATE_MISS_STATS(BINARY_OP);
+                    assert(_PyOpcode_Deopt[opcode] == (BINARY_OP));
+                    JUMP_TO_PREDICTED(BINARY_OP);
+                }
+                if (!_PyLong_IsNonNegativeCompact((PyLongObject *)value_o)) {
                     UPDATE_MISS_STATS(BINARY_OP);
                     assert(_PyOpcode_Deopt[opcode] == (BINARY_OP));
                     JUMP_TO_PREDICTED(BINARY_OP);
@@ -853,9 +858,6 @@
                 assert(PyLong_CheckExact(sub));
                 assert(PyList_CheckExact(list));
                 Py_ssize_t index = _PyLong_CompactValue((PyLongObject *)sub);
-                if (index < 0) {
-                    index += PyList_GET_SIZE(list);
-                }
                 #ifdef Py_GIL_DISABLED
                 _PyFrame_SetStackPointer(frame, stack_pointer);
                 _PyFrame_StackPointerValidate(frame);
@@ -1002,11 +1004,16 @@
             _PyStackRef res;
             _PyStackRef s;
             _PyStackRef i;
-            // _GUARD_TOS_INT
+            // _GUARD_TOS_NON_NEGATIVE_COMPACT_INT
             {
                 value = stack_pointer[-1];
                 PyObject *value_o = PyStackRef_AsPyObjectBorrow(value);
-                if (!_PyLong_CheckExactAndCompact(value_o)) {
+                if (!PyLong_CheckExact(value_o)) {
+                    UPDATE_MISS_STATS(BINARY_OP);
+                    assert(_PyOpcode_Deopt[opcode] == (BINARY_OP));
+                    JUMP_TO_PREDICTED(BINARY_OP);
+                }
+                if (!_PyLong_IsNonNegativeCompact((PyLongObject *)value_o)) {
                     UPDATE_MISS_STATS(BINARY_OP);
                     assert(_PyOpcode_Deopt[opcode] == (BINARY_OP));
                     JUMP_TO_PREDICTED(BINARY_OP);
@@ -1036,11 +1043,6 @@
                 PyObject *str = PyStackRef_AsPyObjectBorrow(str_st);
                 assert(PyLong_CheckExact(sub));
                 assert(PyUnicode_CheckExact(str));
-                if (!_PyLong_IsNonNegativeCompact((PyLongObject*)sub)) {
-                    UPDATE_MISS_STATS(BINARY_OP);
-                    assert(_PyOpcode_Deopt[opcode] == (BINARY_OP));
-                    JUMP_TO_PREDICTED(BINARY_OP);
-                }
                 Py_ssize_t index = ((PyLongObject*)sub)->long_value.ob_digit[0];
                 if (PyUnicode_GET_LENGTH(str) <= index) {
                     UPDATE_MISS_STATS(BINARY_OP);
@@ -1091,11 +1093,16 @@
             _PyStackRef res;
             _PyStackRef ts;
             _PyStackRef ss;
-            // _GUARD_TOS_INT
+            // _GUARD_TOS_NON_NEGATIVE_COMPACT_INT
             {
                 value = stack_pointer[-1];
                 PyObject *value_o = PyStackRef_AsPyObjectBorrow(value);
-                if (!_PyLong_CheckExactAndCompact(value_o)) {
+                if (!PyLong_CheckExact(value_o)) {
+                    UPDATE_MISS_STATS(BINARY_OP);
+                    assert(_PyOpcode_Deopt[opcode] == (BINARY_OP));
+                    JUMP_TO_PREDICTED(BINARY_OP);
+                }
+                if (!_PyLong_IsNonNegativeCompact((PyLongObject *)value_o)) {
                     UPDATE_MISS_STATS(BINARY_OP);
                     assert(_PyOpcode_Deopt[opcode] == (BINARY_OP));
                     JUMP_TO_PREDICTED(BINARY_OP);
@@ -1119,11 +1126,6 @@
                 PyObject *tuple = PyStackRef_AsPyObjectBorrow(tuple_st);
                 assert(PyLong_CheckExact(sub));
                 assert(PyTuple_CheckExact(tuple));
-                if (!_PyLong_IsNonNegativeCompact((PyLongObject *)sub)) {
-                    UPDATE_MISS_STATS(BINARY_OP);
-                    assert(_PyOpcode_Deopt[opcode] == (BINARY_OP));
-                    JUMP_TO_PREDICTED(BINARY_OP);
-                }
                 Py_ssize_t index = ((PyLongObject*)sub)->long_value.ob_digit[0];
                 if (index >= PyTuple_GET_SIZE(tuple)) {
                     UPDATE_MISS_STATS(BINARY_OP);
@@ -1184,11 +1186,16 @@
             _PyStackRef res;
             _PyStackRef s;
             _PyStackRef i;
-            // _GUARD_TOS_INT
+            // _GUARD_TOS_NON_NEGATIVE_COMPACT_INT
             {
                 value = stack_pointer[-1];
                 PyObject *value_o = PyStackRef_AsPyObjectBorrow(value);
-                if (!_PyLong_CheckExactAndCompact(value_o)) {
+                if (!PyLong_CheckExact(value_o)) {
+                    UPDATE_MISS_STATS(BINARY_OP);
+                    assert(_PyOpcode_Deopt[opcode] == (BINARY_OP));
+                    JUMP_TO_PREDICTED(BINARY_OP);
+                }
+                if (!_PyLong_IsNonNegativeCompact((PyLongObject *)value_o)) {
                     UPDATE_MISS_STATS(BINARY_OP);
                     assert(_PyOpcode_Deopt[opcode] == (BINARY_OP));
                     JUMP_TO_PREDICTED(BINARY_OP);
@@ -1213,11 +1220,6 @@
                 PyObject *str = PyStackRef_AsPyObjectBorrow(str_st);
                 assert(PyLong_CheckExact(sub));
                 assert(PyUnicode_CheckExact(str));
-                if (!_PyLong_IsNonNegativeCompact((PyLongObject*)sub)) {
-                    UPDATE_MISS_STATS(BINARY_OP);
-                    assert(_PyOpcode_Deopt[opcode] == (BINARY_OP));
-                    JUMP_TO_PREDICTED(BINARY_OP);
-                }
                 Py_ssize_t index = ((PyLongObject*)sub)->long_value.ob_digit[0];
                 if (PyUnicode_GET_LENGTH(str) <= index) {
                     UPDATE_MISS_STATS(BINARY_OP);
@@ -12750,11 +12752,16 @@
             _PyStackRef sub_st;
             _PyStackRef ls;
             _PyStackRef ss;
-            // _GUARD_TOS_INT
+            // _GUARD_TOS_NON_NEGATIVE_COMPACT_INT
             {
                 value = stack_pointer[-1];
                 PyObject *value_o = PyStackRef_AsPyObjectBorrow(value);
-                if (!_PyLong_CheckExactAndCompact(value_o)) {
+                if (!PyLong_CheckExact(value_o)) {
+                    UPDATE_MISS_STATS(STORE_SUBSCR);
+                    assert(_PyOpcode_Deopt[opcode] == (STORE_SUBSCR));
+                    JUMP_TO_PREDICTED(STORE_SUBSCR);
+                }
+                if (!_PyLong_IsNonNegativeCompact((PyLongObject *)value_o)) {
                     UPDATE_MISS_STATS(STORE_SUBSCR);
                     assert(_PyOpcode_Deopt[opcode] == (STORE_SUBSCR));
                     JUMP_TO_PREDICTED(STORE_SUBSCR);
@@ -12787,10 +12794,7 @@
                     JUMP_TO_PREDICTED(STORE_SUBSCR);
                 }
                 Py_ssize_t len = PyList_GET_SIZE(list);
-                if (index < 0) {
-                    index += len;
-                }
-                if (index < 0 || index >= len) {
+                if (index >= len) {
                     UNLOCK_OBJECT(list);
                     if (true) {
                         UPDATE_MISS_STATS(STORE_SUBSCR);
diff --git a/Python/optimizer_cases.c.h b/Python/optimizer_cases.c.h
index 5e110360b81b44..9060db689bdb76 100644
--- a/Python/optimizer_cases.c.h
+++ b/Python/optimizer_cases.c.h
@@ -1719,6 +1719,10 @@
             break;
         }
 
+        case _GUARD_TOS_NON_NEGATIVE_COMPACT_INT: {
+            break;
+        }
+
         case _STORE_SUBSCR_LIST_INT: {
             JitOptRef sub_st;
             JitOptRef list_st;