diff --git a/src/compiler/checker.ts b/src/compiler/checker.ts
index 77f35376da785..a9d4e0ed50581 100644
--- a/src/compiler/checker.ts
+++ b/src/compiler/checker.ts
@@ -17542,14 +17542,51 @@ export function createTypeChecker(host: TypeCheckerHost): TypeChecker {
         return (deferredGlobalIteratorReturnResultType ||= getGlobalType("IteratorReturnResult" as __String, /*arity*/ 1, reportErrors)) || emptyGenericType;
     }
 
-    function getGlobalDisposableType(reportErrors: boolean) {
+    function _getGlobalDisposableType(reportErrors: boolean) {
         return (deferredGlobalDisposableType ||= getGlobalType("Disposable" as __String, /*arity*/ 0, reportErrors)) || emptyObjectType;
     }
 
-    function getGlobalAsyncDisposableType(reportErrors: boolean) {
+    function _getGlobalAsyncDisposableType(reportErrors: boolean) {
         return (deferredGlobalAsyncDisposableType ||= getGlobalType("AsyncDisposable" as __String, /*arity*/ 0, reportErrors)) || emptyObjectType;
     }
 
+    function checkTypeIsDisposable(type: Type): boolean {
+        if (type.flags & (TypeFlags.Null | TypeFlags.Undefined)) {
+            return true; // null and undefined are allowed
+        }
+
+        // Handle union types
+        if (type.flags & TypeFlags.Union) {
+            return every((type as UnionType).types, checkTypeIsDisposable);
+        }
+
+        const disposePropertyName = getPropertyNameForKnownSymbolName("dispose");
+        const disposeProperty = getPropertyOfType(type, disposePropertyName);
+
+        return !!disposeProperty && !(disposeProperty.flags & SymbolFlags.Optional);
+    }
+
+    function checkTypeIsAsyncDisposable(type: Type): boolean {
+        if (type.flags & (TypeFlags.Null | TypeFlags.Undefined)) {
+            return true; // null and undefined are allowed
+        }
+
+        // Handle union types
+        if (type.flags & TypeFlags.Union) {
+            return every((type as UnionType).types, checkTypeIsAsyncDisposable);
+        }
+
+        const asyncDisposePropertyName = getPropertyNameForKnownSymbolName("asyncDispose");
+        const asyncDisposeProperty = getPropertyOfType(type, asyncDisposePropertyName);
+
+        if (asyncDisposeProperty && !(asyncDisposeProperty.flags & SymbolFlags.Optional)) {
+            return true;
+        }
+
+        // For await using, also check for Symbol.dispose as a fallback
+        return checkTypeIsDisposable(type);
+    }
+
     function getGlobalTypeOrUndefined(name: __String, arity = 0): ObjectType | undefined {
         const symbol = getGlobalSymbol(name, SymbolFlags.Type, /*diagnostic*/ undefined);
         return symbol && getTypeOfGlobalSymbol(symbol, arity) as GenericType;
@@ -44999,18 +45036,13 @@ export function createTypeChecker(host: TypeCheckerHost): TypeChecker {
                     checkTypeAssignableToAndOptionallyElaborate(initializerType, type, node, initializer, /*headMessage*/ undefined);
                     const blockScopeKind = getCombinedNodeFlagsCached(node) & NodeFlags.BlockScoped;
                     if (blockScopeKind === NodeFlags.AwaitUsing) {
-                        const globalAsyncDisposableType = getGlobalAsyncDisposableType(/*reportErrors*/ true);
-                        const globalDisposableType = getGlobalDisposableType(/*reportErrors*/ true);
-                        if (globalAsyncDisposableType !== emptyObjectType && globalDisposableType !== emptyObjectType) {
-                            const optionalDisposableType = getUnionType([globalAsyncDisposableType, globalDisposableType, nullType, undefinedType]);
-                            checkTypeAssignableTo(widenTypeForVariableLikeDeclaration(initializerType, node), optionalDisposableType, initializer, Diagnostics.The_initializer_of_an_await_using_declaration_must_be_either_an_object_with_a_Symbol_asyncDispose_or_Symbol_dispose_method_or_be_null_or_undefined);
+                        if (!checkTypeIsAsyncDisposable(initializerType)) {
+                            error(initializer, Diagnostics.The_initializer_of_an_await_using_declaration_must_be_either_an_object_with_a_Symbol_asyncDispose_or_Symbol_dispose_method_or_be_null_or_undefined);
                         }
                     }
                     else if (blockScopeKind === NodeFlags.Using) {
-                        const globalDisposableType = getGlobalDisposableType(/*reportErrors*/ true);
-                        if (globalDisposableType !== emptyObjectType) {
-                            const optionalDisposableType = getUnionType([globalDisposableType, nullType, undefinedType]);
-                            checkTypeAssignableTo(widenTypeForVariableLikeDeclaration(initializerType, node), optionalDisposableType, initializer, Diagnostics.The_initializer_of_a_using_declaration_must_be_either_an_object_with_a_Symbol_dispose_method_or_be_null_or_undefined);
+                        if (!checkTypeIsDisposable(initializerType)) {
+                            error(initializer, Diagnostics.The_initializer_of_a_using_declaration_must_be_either_an_object_with_a_Symbol_dispose_method_or_be_null_or_undefined);
                         }
                     }
                 }
diff --git a/tests/baselines/reference/usingDeclarationWithGlobalInterfaceModification.errors.txt b/tests/baselines/reference/usingDeclarationWithGlobalInterfaceModification.errors.txt
new file mode 100644
index 0000000000000..d7d0e87434a9b
--- /dev/null
+++ b/tests/baselines/reference/usingDeclarationWithGlobalInterfaceModification.errors.txt
@@ -0,0 +1,34 @@
+usingDeclarationWithGlobalInterfaceModification.ts(26,17): error TS2850: The initializer of a 'using' declaration must be either an object with a '[Symbol.dispose]()' method, or be 'null' or 'undefined'.
+
+
+==== usingDeclarationWithGlobalInterfaceModification.ts (1 errors) ====
+    // Test case that demonstrates the issue from https://github.com/microsoft/TypeScript/issues/62121
+    // When an empty global Disposable interface is declared, it should NOT affect
+    // the checking for Symbol.dispose properties
+    
+    declare global {
+      interface Disposable {}
+    }
+    
+    // This should pass - has Symbol.dispose method
+    const validDisposable = {
+        [Symbol.dispose]() {
+            // disposed
+        }
+    };
+    
+    // This should fail - no Symbol.dispose method
+    const invalidDisposable = {
+        cleanup() {
+            // cleanup
+        }
+    };
+    
+    // With the fix, the checker should directly check for Symbol.dispose properties
+    // rather than relying on assignability to the global Disposable interface
+    using valid = validDisposable;      // should pass
+    using invalid = invalidDisposable;  // should error
+                    ~~~~~~~~~~~~~~~~~
+!!! error TS2850: The initializer of a 'using' declaration must be either an object with a '[Symbol.dispose]()' method, or be 'null' or 'undefined'.
+    
+    export {};
\ No newline at end of file
diff --git a/tests/baselines/reference/usingDeclarationWithGlobalInterfaceModification.js b/tests/baselines/reference/usingDeclarationWithGlobalInterfaceModification.js
new file mode 100644
index 0000000000000..9e2b5f5c398c4
--- /dev/null
+++ b/tests/baselines/reference/usingDeclarationWithGlobalInterfaceModification.js
@@ -0,0 +1,53 @@
+//// [tests/cases/compiler/usingDeclarationWithGlobalInterfaceModification.ts] ////
+
+//// [usingDeclarationWithGlobalInterfaceModification.ts]
+// Test case that demonstrates the issue from https://github.com/microsoft/TypeScript/issues/62121
+// When an empty global Disposable interface is declared, it should NOT affect
+// the checking for Symbol.dispose properties
+
+declare global {
+  interface Disposable {}
+}
+
+// This should pass - has Symbol.dispose method
+const validDisposable = {
+    [Symbol.dispose]() {
+        // disposed
+    }
+};
+
+// This should fail - no Symbol.dispose method
+const invalidDisposable = {
+    cleanup() {
+        // cleanup
+    }
+};
+
+// With the fix, the checker should directly check for Symbol.dispose properties
+// rather than relying on assignability to the global Disposable interface
+using valid = validDisposable;      // should pass
+using invalid = invalidDisposable;  // should error
+
+export {};
+
+//// [usingDeclarationWithGlobalInterfaceModification.js]
+// Test case that demonstrates the issue from https://github.com/microsoft/TypeScript/issues/62121
+// When an empty global Disposable interface is declared, it should NOT affect
+// the checking for Symbol.dispose properties
+// This should pass - has Symbol.dispose method
+const validDisposable = {
+    [Symbol.dispose]() {
+        // disposed
+    }
+};
+// This should fail - no Symbol.dispose method
+const invalidDisposable = {
+    cleanup() {
+        // cleanup
+    }
+};
+// With the fix, the checker should directly check for Symbol.dispose properties
+// rather than relying on assignability to the global Disposable interface
+using valid = validDisposable; // should pass
+using invalid = invalidDisposable; // should error
+export {};
diff --git a/tests/baselines/reference/usingDeclarationWithGlobalInterfaceModification.symbols b/tests/baselines/reference/usingDeclarationWithGlobalInterfaceModification.symbols
new file mode 100644
index 0000000000000..470ef0682f456
--- /dev/null
+++ b/tests/baselines/reference/usingDeclarationWithGlobalInterfaceModification.symbols
@@ -0,0 +1,50 @@
+//// [tests/cases/compiler/usingDeclarationWithGlobalInterfaceModification.ts] ////
+
+=== usingDeclarationWithGlobalInterfaceModification.ts ===
+// Test case that demonstrates the issue from https://github.com/microsoft/TypeScript/issues/62121
+// When an empty global Disposable interface is declared, it should NOT affect
+// the checking for Symbol.dispose properties
+
+declare global {
+>global : Symbol(global, Decl(usingDeclarationWithGlobalInterfaceModification.ts, 0, 0))
+
+  interface Disposable {}
+>Disposable : Symbol(Disposable, Decl(lib.esnext.disposable.d.ts, --, --), Decl(usingDeclarationWithGlobalInterfaceModification.ts, 4, 16))
+}
+
+// This should pass - has Symbol.dispose method
+const validDisposable = {
+>validDisposable : Symbol(validDisposable, Decl(usingDeclarationWithGlobalInterfaceModification.ts, 9, 5))
+
+    [Symbol.dispose]() {
+>[Symbol.dispose] : Symbol([Symbol.dispose], Decl(usingDeclarationWithGlobalInterfaceModification.ts, 9, 25))
+>Symbol.dispose : Symbol(SymbolConstructor.dispose, Decl(lib.esnext.disposable.d.ts, --, --))
+>Symbol : Symbol(Symbol, Decl(lib.es5.d.ts, --, --), Decl(lib.es2015.symbol.d.ts, --, --), Decl(lib.es2015.symbol.wellknown.d.ts, --, --), Decl(lib.es2019.symbol.d.ts, --, --))
+>dispose : Symbol(SymbolConstructor.dispose, Decl(lib.esnext.disposable.d.ts, --, --))
+
+        // disposed
+    }
+};
+
+// This should fail - no Symbol.dispose method
+const invalidDisposable = {
+>invalidDisposable : Symbol(invalidDisposable, Decl(usingDeclarationWithGlobalInterfaceModification.ts, 16, 5))
+
+    cleanup() {
+>cleanup : Symbol(cleanup, Decl(usingDeclarationWithGlobalInterfaceModification.ts, 16, 27))
+
+        // cleanup
+    }
+};
+
+// With the fix, the checker should directly check for Symbol.dispose properties
+// rather than relying on assignability to the global Disposable interface
+using valid = validDisposable;      // should pass
+>valid : Symbol(valid, Decl(usingDeclarationWithGlobalInterfaceModification.ts, 24, 5))
+>validDisposable : Symbol(validDisposable, Decl(usingDeclarationWithGlobalInterfaceModification.ts, 9, 5))
+
+using invalid = invalidDisposable;  // should error
+>invalid : Symbol(invalid, Decl(usingDeclarationWithGlobalInterfaceModification.ts, 25, 5))
+>invalidDisposable : Symbol(invalidDisposable, Decl(usingDeclarationWithGlobalInterfaceModification.ts, 16, 5))
+
+export {};
diff --git a/tests/baselines/reference/usingDeclarationWithGlobalInterfaceModification.types b/tests/baselines/reference/usingDeclarationWithGlobalInterfaceModification.types
new file mode 100644
index 0000000000000..c414b7d5d7e84
--- /dev/null
+++ b/tests/baselines/reference/usingDeclarationWithGlobalInterfaceModification.types
@@ -0,0 +1,65 @@
+//// [tests/cases/compiler/usingDeclarationWithGlobalInterfaceModification.ts] ////
+
+=== usingDeclarationWithGlobalInterfaceModification.ts ===
+// Test case that demonstrates the issue from https://github.com/microsoft/TypeScript/issues/62121
+// When an empty global Disposable interface is declared, it should NOT affect
+// the checking for Symbol.dispose properties
+
+declare global {
+>global : any
+>       : ^^^
+
+  interface Disposable {}
+}
+
+// This should pass - has Symbol.dispose method
+const validDisposable = {
+>validDisposable : { [Symbol.dispose](): void; }
+>                : ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
+>{    [Symbol.dispose]() {        // disposed    }} : { [Symbol.dispose](): void; }
+>                                                   : ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
+
+    [Symbol.dispose]() {
+>[Symbol.dispose] : () => void
+>                 : ^^^^^^^^^^
+>Symbol.dispose : unique symbol
+>               : ^^^^^^^^^^^^^
+>Symbol : SymbolConstructor
+>       : ^^^^^^^^^^^^^^^^^
+>dispose : unique symbol
+>        : ^^^^^^^^^^^^^
+
+        // disposed
+    }
+};
+
+// This should fail - no Symbol.dispose method
+const invalidDisposable = {
+>invalidDisposable : { cleanup(): void; }
+>                  : ^^^^^^^^^^^^^^^^^^^^
+>{    cleanup() {        // cleanup    }} : { cleanup(): void; }
+>                                         : ^^^^^^^^^^^^^^^^^^^^
+
+    cleanup() {
+>cleanup : () => void
+>        : ^^^^^^^^^^
+
+        // cleanup
+    }
+};
+
+// With the fix, the checker should directly check for Symbol.dispose properties
+// rather than relying on assignability to the global Disposable interface
+using valid = validDisposable;      // should pass
+>valid : { [Symbol.dispose](): void; }
+>      : ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
+>validDisposable : { [Symbol.dispose](): void; }
+>                : ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
+
+using invalid = invalidDisposable;  // should error
+>invalid : { cleanup(): void; }
+>        : ^^^^^^^^^^^^^^^^^^^^
+>invalidDisposable : { cleanup(): void; }
+>                  : ^^^^^^^^^^^^^^^^^^^^
+
+export {};
diff --git a/tests/cases/compiler/usingDeclarationWithGlobalInterfaceModification.ts b/tests/cases/compiler/usingDeclarationWithGlobalInterfaceModification.ts
new file mode 100644
index 0000000000000..8b2aba8c5037e
--- /dev/null
+++ b/tests/cases/compiler/usingDeclarationWithGlobalInterfaceModification.ts
@@ -0,0 +1,31 @@
+// @target: esnext
+// @lib: esnext
+
+// Test case that demonstrates the issue from https://github.com/microsoft/TypeScript/issues/62121
+// When an empty global Disposable interface is declared, it should NOT affect
+// the checking for Symbol.dispose properties
+
+declare global {
+  interface Disposable {}
+}
+
+// This should pass - has Symbol.dispose method
+const validDisposable = {
+    [Symbol.dispose]() {
+        // disposed
+    }
+};
+
+// This should fail - no Symbol.dispose method
+const invalidDisposable = {
+    cleanup() {
+        // cleanup
+    }
+};
+
+// With the fix, the checker should directly check for Symbol.dispose properties
+// rather than relying on assignability to the global Disposable interface
+using valid = validDisposable;      // should pass
+using invalid = invalidDisposable;  // should error
+
+export {};
\ No newline at end of file