diff --git a/packages/playground/define/index.html b/packages/playground/define/index.html
index 590d92083c4c21..bf6a9c59689396 100644
--- a/packages/playground/define/index.html
+++ b/packages/playground/define/index.html
@@ -11,6 +11,7 @@ <h1>Define</h1>
 <p>spread array: <code class="spread-array"></code></p>
 
 <script type="module">
+  const __VAR_NAME__ = true // ensure define doesn't replace var name
   text('.exp', __EXP__)
   text('.string', __STRING__)
   text('.number', __NUMBER__)
diff --git a/packages/playground/define/vite.config.js b/packages/playground/define/vite.config.js
index 422f1c4daa9628..848abd09322df6 100644
--- a/packages/playground/define/vite.config.js
+++ b/packages/playground/define/vite.config.js
@@ -15,6 +15,7 @@ module.exports = {
         }
       }
     },
+    __VAR_NAME__: false,
     'process.env.SOMEVAR': '"SOMEVAR"'
   }
 }
diff --git a/packages/vite/src/node/plugins/define.ts b/packages/vite/src/node/plugins/define.ts
index d70eba6fb0deb6..f26df9e4d99405 100644
--- a/packages/vite/src/node/plugins/define.ts
+++ b/packages/vite/src/node/plugins/define.ts
@@ -67,7 +67,8 @@ export function definePlugin(config: ResolvedConfig): Plugin {
             return str.replace(/[-[\]/{}()*+?.\\^$|]/g, '\\$&')
           })
           .join('|') +
-        ')\\b',
+        // prevent trailing assignments
+        ')\\b(?!\\s*?=[^=])',
       'g'
     )