Using a moisturizer with tretinoin is mandatory to reduce irritation risks. There are two ways you could layer your moisturizer when following a tretinoin treatment. To avoid risking irritating your skin, start by using a moisturizer before you layer tretinoin and after it. Sandwiching your tretinoin will most likely keep damage at bay. The best moisturizer to pair with tretinoin is one that aims to repair the skin barrier and has hydrating properties. Tretinoin works best when used with reparative ingredients to reduce the chances of irritation and dryness.