diff --git a/emcc.py b/emcc.py
index 1134bce7f9c9c..1c155d7891fc5 100755
--- a/emcc.py
+++ b/emcc.py
@@ -2866,10 +2866,10 @@ def get_full_import_name(name):
 
   # check if we can address the 2GB mark and higher: either if we start at
   # 2GB, or if we allow growth to either any amount or to 2GB or more.
-  if settings.INITIAL_MEMORY > 2 * 1024 * 1024 * 1024 or \
+  if not settings.MEMORY64 and (settings.INITIAL_MEMORY > 2 * 1024 * 1024 * 1024 or
      (settings.ALLOW_MEMORY_GROWTH and
       (settings.MAXIMUM_MEMORY < 0 or
-       settings.MAXIMUM_MEMORY > 2 * 1024 * 1024 * 1024)):
+       settings.MAXIMUM_MEMORY > 2 * 1024 * 1024 * 1024))):
     settings.CAN_ADDRESS_2GB = 1
 
   settings.EMSCRIPTEN_VERSION = shared.EMSCRIPTEN_VERSION
diff --git a/src/jsifier.js b/src/jsifier.js
index e7f73395b3cd0..80ba7394550b8 100644
--- a/src/jsifier.js
+++ b/src/jsifier.js
@@ -128,7 +128,7 @@ function runJSify() {
       for (let i = 1; i < sig.length; i++) {
         const name = argNames[i - 1];
         if (!name) {
-          error(`convertPointerParams: missing name for argument ${i} in ${symbol}`);
+          error(`handleI64Signatures: missing name for argument ${i} in ${symbol}`);
           return snippet;
         }
         if (WASM_BIGINT) {
@@ -139,6 +139,9 @@ function runJSify() {
           if (sig[i] == 'j' && i53abi) {
             argConvertions += `  ${receiveI64ParamAsI53(name, undefined, false)}\n`;
             newArgs.push(defineI64Param(name));
+          } else if (sig[i] == 'p' && CAN_ADDRESS_2GB) {
+            argConvertions += `  ${name} >>>= 0;\n`;
+            newArgs.push(name);
           } else {
             newArgs.push(name);
           }
@@ -197,8 +200,8 @@ function(${args}) {
 
     const sig = LibraryManager.library[symbol + '__sig'];
     const i53abi = LibraryManager.library[symbol + '__i53abi'];
-    if (sig && ((i53abi && sig.includes('j')) ||
-                (MEMORY64 && sig.includes('p')))) {
+    if (sig &&
+        ((i53abi && sig.includes('j')) || ((MEMORY64 || CAN_ADDRESS_2GB) && sig.includes('p')))) {
       snippet = handleI64Signatures(symbol, snippet, sig, i53abi);
       i53ConversionDeps.forEach((d) => deps.push(d))
     }
diff --git a/src/library.js b/src/library.js
index 57b729c55196b..f9e7aaab57cce 100644
--- a/src/library.js
+++ b/src/library.js
@@ -24,6 +24,10 @@ mergeInto(LibraryManager.library, {
   $ptrToString: (ptr) => {
 #if ASSERTIONS
     assert(typeof ptr === 'number');
+#endif
+#if !CAN_ADDRESS_2GB && !MEMORY64
+    // With CAN_ADDRESS_2GB or MEMORY64, pointers are already unsigned.
+    ptr >>>= 0;
 #endif
     return '0x' + ptr.toString(16).padStart(8, '0');
   },
@@ -199,9 +203,6 @@ mergeInto(LibraryManager.library, {
   emscripten_resize_heap: 'ip',
   emscripten_resize_heap: (requestedSize) => {
     var oldSize = HEAPU8.length;
-#if MEMORY64 != 1
-    requestedSize = requestedSize >>> 0;
-#endif
 #if ALLOW_MEMORY_GROWTH == 0
 #if ABORTING_MALLOC
     abortOnCannotGrowMemory(requestedSize);
@@ -211,6 +212,10 @@ mergeInto(LibraryManager.library, {
 #else // ALLOW_MEMORY_GROWTH == 0
     // With multithreaded builds, races can happen (another thread might increase the size
     // in between), so return a failure, and let the caller retry.
+#if !MEMORY64 && !CAN_ADDRESS_2GB
+    // With CAN_ADDRESS_2GB or MEMORY64, pointers are already unsigned.
+    requestedSize >>>= 0;
+#endif
 #if SHARED_MEMORY
     if (requestedSize <= oldSize) {
       return false;
@@ -3090,7 +3095,6 @@ mergeInto(LibraryManager.library, {
   // Used by wasm-emscripten-finalize to implement STACK_OVERFLOW_CHECK
   __handle_stack_overflow__deps: ['emscripten_stack_get_base', 'emscripten_stack_get_end', '$ptrToString'],
   __handle_stack_overflow: (requested) => {
-    requested = requested >>> 0;
     var base = _emscripten_stack_get_base();
     var end = _emscripten_stack_get_end();
     abort(`stack overflow (Attempt to set SP to ${ptrToString(requested)}` +
@@ -3548,6 +3552,11 @@ mergeInto(LibraryManager.library, {
 #if hasExportedSymbol('emscripten_builtin_memalign')
     size = alignMemory(size, {{{ WASM_PAGE_SIZE }}});
     var ptr = _emscripten_builtin_memalign({{{ WASM_PAGE_SIZE }}}, size);
+#if CAN_ADDRESS_2GB
+    // TODO(sbc): Automate this unsigned convertion when we know that a call
+    // into wasm returns a pointer.
+    ptr >>>= 0;
+#endif
     if (!ptr) return 0;
     return zeroMemory(ptr, size);
 #elif ASSERTIONS
diff --git a/src/library_fs.js b/src/library_fs.js
index da4a1e79bbb2b..55326f3734c6b 100644
--- a/src/library_fs.js
+++ b/src/library_fs.js
@@ -1132,9 +1132,6 @@ FS.staticInit();` +
       return stream.position;
     },
     read: (stream, buffer, offset, length, position) => {
-#if CAN_ADDRESS_2GB
-      offset >>>= 0;
-#endif
       if (length < 0 || position < 0) {
         throw new FS.ErrnoError({{{ cDefs.EINVAL }}});
       }
@@ -1166,9 +1163,6 @@ FS.staticInit();` +
       return bytesRead;
     },
     write: (stream, buffer, offset, length, position, canOwn) => {
-#if CAN_ADDRESS_2GB
-      offset >>>= 0;
-#endif
       if (length < 0 || position < 0) {
         throw new FS.ErrnoError({{{ cDefs.EINVAL }}});
       }
@@ -1242,9 +1236,6 @@ FS.staticInit();` +
       return stream.stream_ops.mmap(stream, length, position, prot, flags);
     },
     msync: (stream, buffer, offset, length, mmapFlags) => {
-#if CAN_ADDRESS_2GB
-      offset >>>= 0;
-#endif
       if (!stream.stream_ops.msync) {
         return 0;
       }
diff --git a/src/library_memfs.js b/src/library_memfs.js
index fc01deae05180..0a78a31773059 100644
--- a/src/library_memfs.js
+++ b/src/library_memfs.js
@@ -105,9 +105,6 @@ mergeInto(LibraryManager.library, {
     // May allocate more, to provide automatic geometric increase and amortized linear performance appending writes.
     // Never shrinks the storage.
     expandFileStorage: function(node, newCapacity) {
-#if CAN_ADDRESS_2GB
-      newCapacity >>>= 0;
-#endif
       var prevCapacity = node.contents ? node.contents.length : 0;
       if (prevCapacity >= newCapacity) return; // No need to expand, the storage was already large enough.
       // Don't expand strictly to the given requested limit if it's only a very small increase, but instead geometrically grow capacity.
@@ -123,9 +120,6 @@ mergeInto(LibraryManager.library, {
 
     // Performs an exact resize of the backing file storage to the given size, if the size is not exactly this, the storage is fully reallocated.
     resizeFileStorage: function(node, newSize) {
-#if CAN_ADDRESS_2GB
-      newSize >>>= 0;
-#endif
       if (node.usedBytes == newSize) return;
       if (newSize == 0) {
         node.contents = null; // Fully decommit when requesting a resize to zero.
@@ -360,9 +354,6 @@ mergeInto(LibraryManager.library, {
           if (!ptr) {
             throw new FS.ErrnoError({{{ cDefs.ENOMEM }}});
           }
-#if CAN_ADDRESS_2GB
-          ptr >>>= 0;
-#endif
           HEAP8.set(contents, ptr);
         }
         return { ptr, allocated };
diff --git a/src/library_strings.js b/src/library_strings.js
index 6110ba8bb171f..1ad54072971f7 100644
--- a/src/library_strings.js
+++ b/src/library_strings.js
@@ -27,9 +27,6 @@ mergeInto(LibraryManager.library, {
   $UTF8ArrayToString__deps: ['$UTF8Decoder'],
 #endif
   $UTF8ArrayToString: (heapOrArray, idx, maxBytesToRead) => {
-#if CAN_ADDRESS_2GB
-    idx >>>= 0;
-#endif
     var endIdx = idx + maxBytesToRead;
 #if TEXTDECODER
     var endPtr = idx;
@@ -118,9 +115,6 @@ mergeInto(LibraryManager.library, {
 #if ASSERTIONS
     assert(typeof ptr == 'number');
 #endif
-#if CAN_ADDRESS_2GB
-    ptr >>>= 0;
-#endif
 #if TEXTDECODER == 2
     if (!ptr) return '';
     var maxPtr = ptr + maxBytesToRead;
@@ -154,9 +148,6 @@ mergeInto(LibraryManager.library, {
    * @return {number} The number of bytes written, EXCLUDING the null terminator.
    */
   $stringToUTF8Array: (str, heap, outIdx, maxBytesToWrite) => {
-#if CAN_ADDRESS_2GB
-    outIdx >>>= 0;
-#endif
 #if ASSERTIONS
     assert(typeof str === 'string');
 #endif
@@ -262,9 +253,6 @@ mergeInto(LibraryManager.library, {
   // emscripten HEAP, returns a copy of that string as a Javascript String
   // object.
   $AsciiToString: (ptr) => {
-#if CAN_ADDRESS_2GB
-    ptr >>>= 0;
-#endif
     var str = '';
     while (1) {
       var ch = {{{ makeGetValue('ptr++', 0, 'u8') }}};
@@ -429,9 +417,6 @@ mergeInto(LibraryManager.library, {
   //                    output, not even the null terminator.
   // Returns the number of bytes written, EXCLUDING the null terminator.
   $stringToUTF32: (str, outPtr, maxBytesToWrite) => {
-#if CAN_ADDRESS_2GB
-    outPtr >>>= 0;
-#endif
 #if ASSERTIONS
     assert(outPtr % 4 == 0, 'Pointer passed to stringToUTF32 must be aligned to four bytes!');
 #endif
diff --git a/src/library_syscall.js b/src/library_syscall.js
index 40ab08e493021..df30beb1c2d73 100644
--- a/src/library_syscall.js
+++ b/src/library_syscall.js
@@ -80,9 +80,6 @@ var SyscallsLibrary = {
         // MAP_PRIVATE calls need not to be synced back to underlying fs
         return 0;
       }
-#if CAN_ADDRESS_2GB
-      addr >>>= 0;
-#endif
       var buffer = HEAPU8.slice(addr, addr + len);
       FS.msync(stream, buffer, offset, len, flags);
     },
@@ -142,9 +139,6 @@ var SyscallsLibrary = {
     var res = FS.mmap(stream, len, offset, prot, flags);
     var ptr = res.ptr;
     {{{ makeSetValue('allocated', 0, 'res.allocated', 'i32') }}};
-#if CAN_ADDRESS_2GB
-    ptr >>>= 0;
-#endif
     {{{ makeSetValue('addr', 0, 'ptr', '*') }}};
     return 0;
 #else // no filesystem support; report lack of support
diff --git a/src/library_webgpu.js b/src/library_webgpu.js
index c84e5a6ea5934..2c60f5184614b 100644
--- a/src/library_webgpu.js
+++ b/src/library_webgpu.js
@@ -1841,7 +1841,6 @@ var LibraryWebGPU = {
 
     if (size === 0) warnOnce('getMappedRange size=0 no longer means WGPU_WHOLE_MAP_SIZE');
 
-    size = size >>> 0;
     if (size === {{{ gpu.WHOLE_MAP_SIZE }}}) size = undefined;
 
     var mapped;
@@ -1875,7 +1874,6 @@ var LibraryWebGPU = {
 
     if (size === 0) warnOnce('getMappedRange size=0 no longer means WGPU_WHOLE_MAP_SIZE');
 
-    size = size >>> 0;
     if (size === {{{ gpu.WHOLE_MAP_SIZE }}}) size = undefined;
 
     if (bufferWrapper.mapMode !== {{{ gpu.MapMode.Write }}}) {
@@ -1916,7 +1914,6 @@ var LibraryWebGPU = {
     bufferWrapper.onUnmap = [];
     var buffer = bufferWrapper.object;
 
-    size = size >>> 0;
     if (size === {{{ gpu.WHOLE_MAP_SIZE }}}) size = undefined;
 
     // `callback` takes (WGPUBufferMapAsyncStatus status, void * userdata)
diff --git a/src/settings_internal.js b/src/settings_internal.js
index b9cb0ea0fc404..82ca320dbf1b2 100644
--- a/src/settings_internal.js
+++ b/src/settings_internal.js
@@ -186,8 +186,14 @@ var WASM_SYSTEM_EXPORTS = ['stackAlloc', 'stackSave', 'stackRestore', 'getTempRe
 // Internal: value of -flto argument (either full or thin)
 var LTO = 0;
 
-// Whether we may be accessing the address 2GB or higher. If so then we need
-// to be using unsigned pointers in JS.
+// Whether we may be accessing the address 2GB or higher. If so, then we need
+// to interpret incoming i32 pointers as unsigned when they arrive in JS.
+// In most cases this taken care of automatically based on the `__sig` of JS
+// library functions.
+//
+// This setting does not apply (and is never set to true) unser MEMORY64, since
+// in that case we get 64-bit pointers coming throught to JS (converting them to
+// i53 in most cases.
 var CAN_ADDRESS_2GB = false;
 
 // Whether to emit DWARF in a separate wasm file on the side (this is not called
diff --git a/test/other/metadce/test_metadce_mem_O3_grow.jssize b/test/other/metadce/test_metadce_mem_O3_grow.jssize
index 9d89391e19f5c..230ddc863bca0 100644
--- a/test/other/metadce/test_metadce_mem_O3_grow.jssize
+++ b/test/other/metadce/test_metadce_mem_O3_grow.jssize
@@ -1 +1 @@
-6195
+6188