diff --git a/Include/internal/pycore_code.h b/Include/internal/pycore_code.h
index 5b1fddbe15b98b..6673a5df9a4170 100644
--- a/Include/internal/pycore_code.h
+++ b/Include/internal/pycore_code.h
@@ -540,7 +540,7 @@ typedef struct {
 PyAPI_FUNC(int) _Py_Instrument(PyCodeObject *co, PyInterpreterState *interp);
 
 // Export for '_testinternalcapi' shared extension
-PyAPI_FUNC(_Py_CODEUNIT) _Py_GetBaseCodeUnit(PyCodeObject *code, int offset);
+PyAPI_FUNC(_Py_CODEUNIT) _Py_GetBaseCodeUnit(PyCodeObject *code, Py_ssize_t offset);
 
 extern int _PyInstruction_GetLength(PyCodeObject *code, int offset);
 
diff --git a/Include/internal/pycore_instruments.h b/Include/internal/pycore_instruments.h
index 56b55e93a014cb..d134064d9ca24b 100644
--- a/Include/internal/pycore_instruments.h
+++ b/Include/internal/pycore_instruments.h
@@ -122,7 +122,7 @@ extern int
 _Py_Instrumentation_GetLine(PyCodeObject *code, _PyCoLineInstrumentationData *line_data, int index);
 
 static inline uint8_t
-_PyCode_GetOriginalOpcode(_PyCoLineInstrumentationData *line_data, int index)
+_PyCode_GetOriginalOpcode(_PyCoLineInstrumentationData *line_data, Py_ssize_t index)
 {
     return line_data->data[index*line_data->bytes_per_entry];
 }
diff --git a/Modules/_testinternalcapi/test_cases.c.h b/Modules/_testinternalcapi/test_cases.c.h
index 238e17bea303d3..dcc2b9ef7fa54f 100644
--- a/Modules/_testinternalcapi/test_cases.c.h
+++ b/Modules/_testinternalcapi/test_cases.c.h
@@ -7946,7 +7946,8 @@
                 assert(INLINE_CACHE_ENTRIES_SEND == INLINE_CACHE_ENTRIES_FOR_ITER);
                 #if TIER_ONE && defined(Py_DEBUG)
                 if (!PyStackRef_IsNone(frame->f_executable)) {
-                    int i = frame->instr_ptr - _PyFrame_GetBytecode(frame);
+                    Py_ssize_t i = frame->instr_ptr - _PyFrame_GetBytecode(frame);
+                    assert(i > 0);
                     int opcode = _Py_GetBaseCodeUnit(_PyFrame_GetCode(frame), i).op.code;
                     assert(opcode == SEND || opcode == FOR_ITER);
                 }
@@ -13056,7 +13057,8 @@
                 assert(INLINE_CACHE_ENTRIES_SEND == INLINE_CACHE_ENTRIES_FOR_ITER);
                 #if TIER_ONE && defined(Py_DEBUG)
                 if (!PyStackRef_IsNone(frame->f_executable)) {
-                    int i = frame->instr_ptr - _PyFrame_GetBytecode(frame);
+                    Py_ssize_t i = frame->instr_ptr - _PyFrame_GetBytecode(frame);
+                    assert(i > 0);
                     int opcode = _Py_GetBaseCodeUnit(_PyFrame_GetCode(frame), i).op.code;
                     assert(opcode == SEND || opcode == FOR_ITER);
                 }
diff --git a/Python/bytecodes.c b/Python/bytecodes.c
index 3bd489122da9d4..cf7a56c95ff600 100644
--- a/Python/bytecodes.c
+++ b/Python/bytecodes.c
@@ -1867,7 +1867,8 @@ dummy_func(
             assert(INLINE_CACHE_ENTRIES_SEND == INLINE_CACHE_ENTRIES_FOR_ITER);
             #if TIER_ONE && defined(Py_DEBUG)
             if (!PyStackRef_IsNone(frame->f_executable)) {
-                int i = frame->instr_ptr - _PyFrame_GetBytecode(frame);
+                Py_ssize_t i = frame->instr_ptr - _PyFrame_GetBytecode(frame);
+                assert(i > 0);
                 int opcode = _Py_GetBaseCodeUnit(_PyFrame_GetCode(frame), i).op.code;
                 assert(opcode == SEND || opcode == FOR_ITER);
             }
diff --git a/Python/executor_cases.c.h b/Python/executor_cases.c.h
index b6a2821db3007e..67219fc9c61a05 100644
--- a/Python/executor_cases.c.h
+++ b/Python/executor_cases.c.h
@@ -9346,7 +9346,8 @@
             assert(INLINE_CACHE_ENTRIES_SEND == INLINE_CACHE_ENTRIES_FOR_ITER);
             #if TIER_ONE && defined(Py_DEBUG)
             if (!PyStackRef_IsNone(frame->f_executable)) {
-                int i = frame->instr_ptr - _PyFrame_GetBytecode(frame);
+                Py_ssize_t i = frame->instr_ptr - _PyFrame_GetBytecode(frame);
+                assert(i > 0);
                 int opcode = _Py_GetBaseCodeUnit(_PyFrame_GetCode(frame), i).op.code;
                 assert(opcode == SEND || opcode == FOR_ITER);
             }
diff --git a/Python/generated_cases.c.h b/Python/generated_cases.c.h
index 2623105656c90c..61d1bb5ec18324 100644
--- a/Python/generated_cases.c.h
+++ b/Python/generated_cases.c.h
@@ -7945,7 +7945,8 @@
                 assert(INLINE_CACHE_ENTRIES_SEND == INLINE_CACHE_ENTRIES_FOR_ITER);
                 #if TIER_ONE && defined(Py_DEBUG)
                 if (!PyStackRef_IsNone(frame->f_executable)) {
-                    int i = frame->instr_ptr - _PyFrame_GetBytecode(frame);
+                    Py_ssize_t i = frame->instr_ptr - _PyFrame_GetBytecode(frame);
+                    assert(i > 0);
                     int opcode = _Py_GetBaseCodeUnit(_PyFrame_GetCode(frame), i).op.code;
                     assert(opcode == SEND || opcode == FOR_ITER);
                 }
@@ -13053,7 +13054,8 @@
                 assert(INLINE_CACHE_ENTRIES_SEND == INLINE_CACHE_ENTRIES_FOR_ITER);
                 #if TIER_ONE && defined(Py_DEBUG)
                 if (!PyStackRef_IsNone(frame->f_executable)) {
-                    int i = frame->instr_ptr - _PyFrame_GetBytecode(frame);
+                    Py_ssize_t i = frame->instr_ptr - _PyFrame_GetBytecode(frame);
+                    assert(i > 0);
                     int opcode = _Py_GetBaseCodeUnit(_PyFrame_GetCode(frame), i).op.code;
                     assert(opcode == SEND || opcode == FOR_ITER);
                 }
diff --git a/Python/instrumentation.c b/Python/instrumentation.c
index 51bcbfdb3b6c55..00ac171658815e 100644
--- a/Python/instrumentation.c
+++ b/Python/instrumentation.c
@@ -635,7 +635,7 @@ sanity_check_instrumentation(PyCodeObject *code)
 
 /* Get the underlying code unit, stripping instrumentation and ENTER_EXECUTOR */
 _Py_CODEUNIT
-_Py_GetBaseCodeUnit(PyCodeObject *code, int i)
+_Py_GetBaseCodeUnit(PyCodeObject *code, Py_ssize_t i)
 {
     _Py_CODEUNIT *src_instr = _PyCode_CODE(code) + i;
     _Py_CODEUNIT inst = {