diff --git a/plugins/web/opentelemetry-instrumentation-user-interaction/src/instrumentation.ts b/plugins/web/opentelemetry-instrumentation-user-interaction/src/instrumentation.ts
index da499ec1a9..cac04f49d5 100644
--- a/plugins/web/opentelemetry-instrumentation-user-interaction/src/instrumentation.ts
+++ b/plugins/web/opentelemetry-instrumentation-user-interaction/src/instrumentation.ts
@@ -330,6 +330,24 @@ export class UserInteractionInstrumentation extends InstrumentationBase<unknown>
     };
   }
 
+  /**
+   * Most browser provide event listener api via EventTarget in prototype chain.
+   * Exception to this is IE 11 which has it on the prototypes closest to EventTarget:
+   *
+   * * - has addEventListener in IE
+   * ** - has addEventListener in all other browsers
+   * ! - missing in IE
+   *
+   * HTMLElement -> Element -> Node * -> EventTarget **! -> Object
+   * Document -> Node * -> EventTarget **! -> Object
+   * Window * -> WindowProperties ! -> EventTarget **! -> Object
+   */
+  private _getPatchableEventTargets(): EventTarget[] {
+    return window.EventTarget
+      ? [EventTarget.prototype]
+      : [Node.prototype, Window.prototype];
+  }
+
   /**
    * Patches the history api
    */
@@ -571,26 +589,27 @@ export class UserInteractionInstrumentation extends InstrumentationBase<unknown>
       );
     } else {
       this._zonePatched = false;
-      if (isWrapped(EventTarget.prototype.addEventListener)) {
-        this._unwrap(EventTarget.prototype, 'addEventListener');
-        api.diag.debug('removing previous patch from method addEventListener');
-      }
-      if (isWrapped(EventTarget.prototype.removeEventListener)) {
-        this._unwrap(EventTarget.prototype, 'removeEventListener');
-        api.diag.debug(
-          'removing previous patch from method removeEventListener'
+      const targets = this._getPatchableEventTargets();
+      targets.forEach(target => {
+        if (isWrapped(target.addEventListener)) {
+          this._unwrap(target, 'addEventListener');
+          api.diag.debug(
+            'removing previous patch from method addEventListener'
+          );
+        }
+        if (isWrapped(target.removeEventListener)) {
+          this._unwrap(target, 'removeEventListener');
+          api.diag.debug(
+            'removing previous patch from method removeEventListener'
+          );
+        }
+        this._wrap(target, 'addEventListener', this._patchAddEventListener());
+        this._wrap(
+          target,
+          'removeEventListener',
+          this._patchRemoveEventListener()
         );
-      }
-      this._wrap(
-        EventTarget.prototype,
-        'addEventListener',
-        this._patchAddEventListener()
-      );
-      this._wrap(
-        EventTarget.prototype,
-        'removeEventListener',
-        this._patchRemoveEventListener()
-      );
+      });
     }
 
     this._patchHistoryApi();
@@ -619,12 +638,15 @@ export class UserInteractionInstrumentation extends InstrumentationBase<unknown>
         this._unwrap(ZoneWithPrototype.prototype, 'cancelTask');
       }
     } else {
-      if (isWrapped(HTMLElement.prototype.addEventListener)) {
-        this._unwrap(HTMLElement.prototype, 'addEventListener');
-      }
-      if (isWrapped(HTMLElement.prototype.removeEventListener)) {
-        this._unwrap(HTMLElement.prototype, 'removeEventListener');
-      }
+      const targets = this._getPatchableEventTargets();
+      targets.forEach(target => {
+        if (isWrapped(target.addEventListener)) {
+          this._unwrap(target, 'addEventListener');
+        }
+        if (isWrapped(target.removeEventListener)) {
+          this._unwrap(target, 'removeEventListener');
+        }
+      });
     }
     this._unpatchHistoryApi();
   }
diff --git a/plugins/web/opentelemetry-instrumentation-user-interaction/test/userInteraction.nozone.test.ts b/plugins/web/opentelemetry-instrumentation-user-interaction/test/userInteraction.nozone.test.ts
index 08447543be..38c3cd240b 100644
--- a/plugins/web/opentelemetry-instrumentation-user-interaction/test/userInteraction.nozone.test.ts
+++ b/plugins/web/opentelemetry-instrumentation-user-interaction/test/userInteraction.nozone.test.ts
@@ -619,5 +619,42 @@ describe('UserInteractionInstrumentation', () => {
         'go should be unwrapped'
       );
     });
+
+    describe('simulate IE', () => {
+      // Save window.EventTarget reference (including enumerable state)
+      const EventTargetDesc = Object.getOwnPropertyDescriptor(
+        window,
+        'EventTarget'
+      )!;
+      before(() => {
+        // @ts-expect-error window.EventTarget not optional
+        delete window.EventTarget;
+      });
+      after(() => {
+        Object.defineProperty(window, 'EventTarget', EventTargetDesc);
+        // Undo unwrap putting originals back on it's targets
+        // @ts-expect-error event listener API not optional
+        delete Node.prototype.addEventListener;
+        // @ts-expect-error copy
+        delete Node.prototype.removeEventListener;
+        // @ts-expect-error copy
+        delete Window.prototype.addEventListener;
+        // @ts-expect-error copy
+        delete Window.prototype.removeEventListener;
+      });
+
+      it('works with missing EventTarget', () => {
+        /*
+         * Would already error out with:
+         * "before each" hook for "works with missing EventTarget"
+         *   ReferenceError: EventTarget is not defined
+         */
+
+        fakeInteraction();
+        assert.equal(exportSpy.args.length, 1, 'should export one span');
+        const spanClick = exportSpy.args[0][0][0];
+        assertClickSpan(spanClick);
+      });
+    });
   });
 });