diff --git a/packages/vite/src/node/plugins/esbuild.ts b/packages/vite/src/node/plugins/esbuild.ts
index 591e2883453fe3..d2bf848437a915 100644
--- a/packages/vite/src/node/plugins/esbuild.ts
+++ b/packages/vite/src/node/plugins/esbuild.ts
@@ -28,9 +28,10 @@ import { searchForWorkspaceRoot } from '../server/searchRoot'
 
 const debug = createDebugger('vite:esbuild')
 
-// IIFE content looks like `var MyLib = function() {`. Spaces are removed when minified
-const IIFE_BEGIN_RE =
-  /(const|var)\s+\S+\s*=\s*function\(\)\s*\{.*"use strict";/s
+const INJECT_HELPERS_IIFE_RE =
+  /^(.*?)((?:const|var)\s+\S+\s*=\s*function\s*\([^)]*\)\s*\{\s*"use strict";)/s
+const INJECT_HELPERS_UMD_RE =
+  /^(.*?)(\(function\([^)]*\)\s*\{.+?amd.+?function\([^)]*\)\s*\{\s*"use strict";)/s
 
 const validExtensionRE = /\.\w+$/
 const jsxExtensionsRE = /\.(?:j|t)sx\b/
@@ -332,30 +333,22 @@ export const buildEsbuildPlugin = (config: ResolvedConfig): Plugin => {
       if (config.build.lib) {
         // #7188, esbuild adds helpers out of the UMD and IIFE wrappers, and the
         // names are minified potentially causing collision with other globals.
-        // We inject the helpers inside the wrappers.
-        // e.g. turn:
-        //    <esbuild helpers> (function(){ /*actual content/* })()
-        // into:
-        //    (function(){ <esbuild helpers> /*actual content/* })()
-        // Not using regex because it's too hard to rule out performance issues like #8738 #8099 #10900 #14065
-        // Instead, using plain string index manipulation (indexOf, slice) which is simple and performant
+        // We use a regex to inject the helpers inside the wrappers.
         // We don't need to create a MagicString here because both the helpers and
         // the headers don't modify the sourcemap
-        const esbuildCode = res.code
-        const contentIndex =
-          opts.format === 'iife'
-            ? esbuildCode.match(IIFE_BEGIN_RE)?.index || 0
-            : opts.format === 'umd'
-            ? esbuildCode.indexOf(`(function(`) // same for minified or not
-            : 0
-        if (contentIndex > 0) {
-          const esbuildHelpers = esbuildCode.slice(0, contentIndex)
-          res.code = esbuildCode
-            .slice(contentIndex)
-            .replace(`"use strict";`, `"use strict";` + esbuildHelpers)
+        const injectHelpers =
+          opts.format === 'umd'
+            ? INJECT_HELPERS_UMD_RE
+            : opts.format === 'iife'
+            ? INJECT_HELPERS_IIFE_RE
+            : undefined
+        if (injectHelpers) {
+          res.code = res.code.replace(
+            injectHelpers,
+            (_, helpers, header) => header + helpers,
+          )
         }
       }
-
       return res
     },
   }
diff --git a/playground/lib/__tests__/lib.spec.ts b/playground/lib/__tests__/lib.spec.ts
index 8232a2fd100649..b203535e0154da 100644
--- a/playground/lib/__tests__/lib.spec.ts
+++ b/playground/lib/__tests__/lib.spec.ts
@@ -33,9 +33,7 @@ describe.runIf(isBuild)('build', () => {
       'dist/nominify/my-lib-custom-filename.iife.js',
     )
     // esbuild helpers are injected inside of the IIFE wrapper
-    // esbuild has a bug that injects some statements before `"use strict"`: https://github.com/evanw/esbuild/issues/3322
-    // remove the `.*?` part once it's fixed
-    expect(code).toMatch(/^var MyLib=function\(\)\{.*?"use strict";/)
+    expect(code).toMatch(/^var MyLib=function\(\)\{"use strict";/)
     expect(noMinifyCode).toMatch(
       /^var MyLib\s*=\s*function\(\)\s*\{.*?"use strict";/s,
     )
diff --git a/playground/lib/src/main.js b/playground/lib/src/main.js
index 8be8ec37e635ee..59c8e897cb0789 100644
--- a/playground/lib/src/main.js
+++ b/playground/lib/src/main.js
@@ -10,6 +10,3 @@ export default function myLib(sel) {
   // make sure umd helper has been moved to the right position
   console.log(`amd function(){ "use strict"; }`)
 }
-
-// For triggering unhandled global esbuild helpers in previous regex-based implementation for injection
-;(function () {})()?.foo
diff --git a/playground/lib/vite.config.js b/playground/lib/vite.config.js
index 84612ba1f65306..6b4395624dc27a 100644
--- a/playground/lib/vite.config.js
+++ b/playground/lib/vite.config.js
@@ -7,7 +7,6 @@ export default defineConfig({
     supported: {
       // Force esbuild inject helpers to test regex
       'object-rest-spread': false,
-      'optional-chain': false,
     },
   },
   build: {