I can’t see why not. I’ve used Smarty with AJAX in the past, though not for a few years now. The simple solution is often to render a block from a page, rather than an entire page (ie don’t render the header and footer), and send that block in your AJAX response and using JS (whether directly or via jQuery or similar) replace/append the HTML that you received. There’s no reason why a server-side template engine should have any bearing on the front-end code