Topical (applied to the skin) pain relievers treat OA pain locally without most of the side effects that go along with taking medications by mouth. Medications that may be applied topically include NSAIDs, capsaicin, methyl salicylate, and trolamine salicylate. Topical diclofenac (an NSAID) is available as drops and is approved for relieving symptoms of OA of the knee, including stiffness. The other topical pain relievers for OA can also be used in combination with other treatments as a means to improve the control of OA symptoms.

Side effects with topical medications are normally limited to the areas where they are applied. Capsaicin must be applied regularly 3 to 4 times per day to overcome the tingling, burning, or redness that usually occurs when starting the treatment. Methyl salicylate and trolamine salicylate may cause an allergic reaction when applied; people allergic to ASA should avoid these topical agents. The possibility of increased risk for bleeding exists when topical NSAIDs and salicylates are used by people taking anticoagulants such as warfarin.