diff --git a/experimental/CHANGELOG.md b/experimental/CHANGELOG.md
index c8db9ca78a6..06491883f5c 100644
--- a/experimental/CHANGELOG.md
+++ b/experimental/CHANGELOG.md
@@ -16,6 +16,7 @@ All notable changes to experimental packages in this project will be documented
 
 * fix(instrumentation-xhr): http.url attribute should be absolute [#3200](https://github.com/open-telemetry/opentelemetry-js/pull/3200) @t2t2
 * fix(instrumentation-grpc): always set grpc semcov status code attribute with numeric value [#3076](https://github.com/open-telemetry/opentelemetry-js/pull/3076) @blumamir
+* fix(instrumentation): only call `onRequire` for full matches on core modules with sub-paths [#3451](https://github.com/open-telemetry/opentelemetry-js/pull/3451) @mhassan1
 * fix(instrumentation): add back support for absolute paths via `require-in-the-middle` [#3457](https://github.com/open-telemetry/opentelemetry-js/pull/3457) @mhassan1
 
 ### :books: (Refine Doc)
diff --git a/experimental/packages/opentelemetry-instrumentation/src/platform/node/ModuleNameTrie.ts b/experimental/packages/opentelemetry-instrumentation/src/platform/node/ModuleNameTrie.ts
index 19b3e0912ae..e971421cda0 100644
--- a/experimental/packages/opentelemetry-instrumentation/src/platform/node/ModuleNameTrie.ts
+++ b/experimental/packages/opentelemetry-instrumentation/src/platform/node/ModuleNameTrie.ts
@@ -26,6 +26,17 @@ class ModuleNameTrieNode {
   children: Map<string, ModuleNameTrieNode> = new Map();
 }
 
+type ModuleNameTrieSearchOptions = {
+  /**
+   * Whether to return the results in insertion order
+   */
+  maintainInsertionOrder?: boolean;
+  /**
+   * Whether to return only full matches
+   */
+  fullOnly?: boolean;
+};
+
 /**
  * Trie containing nodes that represent a part of a module name (i.e. the parts separated by forward slash)
  */
@@ -57,24 +68,33 @@ export class ModuleNameTrie {
    *
    * @param {string} moduleName Module name
    * @param {boolean} maintainInsertionOrder Whether to return the results in insertion order
+   * @param {boolean} fullOnly Whether to return only full matches
    * @returns {Hooked[]} Matching hooks
    */
   search(
     moduleName: string,
-    { maintainInsertionOrder }: { maintainInsertionOrder?: boolean } = {}
+    { maintainInsertionOrder, fullOnly }: ModuleNameTrieSearchOptions = {}
   ): Hooked[] {
     let trieNode = this._trie;
     const results: ModuleNameTrieNode['hooks'] = [];
+    let foundFull = true;
 
     for (const moduleNamePart of moduleName.split(ModuleNameSeparator)) {
       const nextNode = trieNode.children.get(moduleNamePart);
       if (!nextNode) {
+        foundFull = false;
         break;
       }
-      results.push(...nextNode.hooks);
+      if (!fullOnly) {
+        results.push(...nextNode.hooks);
+      }
       trieNode = nextNode;
     }
 
+    if (fullOnly && foundFull) {
+      results.push(...trieNode.hooks);
+    }
+
     if (results.length === 0) {
       return [];
     }
diff --git a/experimental/packages/opentelemetry-instrumentation/src/platform/node/RequireInTheMiddleSingleton.ts b/experimental/packages/opentelemetry-instrumentation/src/platform/node/RequireInTheMiddleSingleton.ts
index 76089a142fc..0bcea53ea8b 100644
--- a/experimental/packages/opentelemetry-instrumentation/src/platform/node/RequireInTheMiddleSingleton.ts
+++ b/experimental/packages/opentelemetry-instrumentation/src/platform/node/RequireInTheMiddleSingleton.ts
@@ -69,6 +69,10 @@ export class RequireInTheMiddleSingleton {
 
         const matches = this._moduleNameTrie.search(normalizedModuleName, {
           maintainInsertionOrder: true,
+          // For core modules (e.g. `fs`), do not match on sub-paths (e.g. `fs/promises').
+          // This matches the behavior of `require-in-the-middle`.
+          // `basedir` is always `undefined` for core modules.
+          fullOnly: basedir === undefined,
         });
 
         for (const { onRequire } of matches) {
diff --git a/experimental/packages/opentelemetry-instrumentation/test/node/ModuleNameTrie.test.ts b/experimental/packages/opentelemetry-instrumentation/test/node/ModuleNameTrie.test.ts
index 7418722e26d..304aae996c5 100644
--- a/experimental/packages/opentelemetry-instrumentation/test/node/ModuleNameTrie.test.ts
+++ b/experimental/packages/opentelemetry-instrumentation/test/node/ModuleNameTrie.test.ts
@@ -61,5 +61,27 @@ describe('ModuleNameTrie', () => {
         ]);
       });
     });
+
+    describe('fullOnly = false', () => {
+      it('should return a list of matches for prefixes', () => {
+        assert.deepEqual(trie.search('a/b'), [
+          inserts[0],
+          inserts[2],
+          inserts[1],
+        ]);
+      });
+    });
+
+    describe('fullOnly = true', () => {
+      it('should return a list of matches for full values only', () => {
+        assert.deepEqual(trie.search('a', { fullOnly: true }), [
+          inserts[0],
+          inserts[2],
+        ]);
+        assert.deepEqual(trie.search('a/b', { fullOnly: true }), [inserts[1]]);
+        assert.deepEqual(trie.search('e', { fullOnly: true }), []);
+        assert.deepEqual(trie.search('a/b/e', { fullOnly: true }), []);
+      });
+    });
   });
 });
diff --git a/experimental/packages/opentelemetry-instrumentation/test/node/RequireInTheMiddleSingleton.test.ts b/experimental/packages/opentelemetry-instrumentation/test/node/RequireInTheMiddleSingleton.test.ts
index 8fddad45984..df7059987cb 100644
--- a/experimental/packages/opentelemetry-instrumentation/test/node/RequireInTheMiddleSingleton.test.ts
+++ b/experimental/packages/opentelemetry-instrumentation/test/node/RequireInTheMiddleSingleton.test.ts
@@ -106,22 +106,14 @@ describe('RequireInTheMiddleSingleton', () => {
       describe('AND module name matches', () => {
         it('should call `onRequire`', () => {
           const exports = require('fs/promises');
-          assert.deepStrictEqual(exports.__ritmOnRequires, [
-            'fs',
-            'fs-promises',
-          ]);
+          assert.deepStrictEqual(exports.__ritmOnRequires, ['fs-promises']);
           sinon.assert.calledOnceWithExactly(
             onRequireFsPromisesStub,
             exports,
             'fs/promises',
             undefined
           );
-          sinon.assert.calledOnceWithMatch(
-            onRequireFsStub,
-            { __ritmOnRequires: ['fs', 'fs-promises'] },
-            'fs/promises',
-            undefined
-          );
+          sinon.assert.notCalled(onRequireFsStub);
         });
       });
     });