Background: Surgical procedures used to remove genital warts (cryotherapy, electrodesiccation) are painful. Attempts to reduce the discomfort of surgery by prior lidocaine infiltration anesthesia are compromised by the pain of the infiltration. Objective: Our purpose was to determine the efficacy of topically applied lidocaine/prilocaine cream to reduce the pain of lidocaine infiltration and the pain associated with cryotherapy to remove genital warts. Methods: Men, scheduled for removal of genital warts by cryotherapy, were randomly selected to receive one of three treatments: (1) lidocaine/prilocaine cream application, (2) 1% lidocaine infiltration, and (3) lidocaine/prilocaine cream application followed by infiltration of 1% lidocaine. Results: Application of lidocaine/prilocaine cream for 15 minutes markedly reduced the pain of lidocaine infiltration. The combination of lidocaine/prilocaine cream followed by infiltration of 1% lidocaine gave greater pain relief from the cryotherapy than did either anesthetic alone. Conclusion: The application of lidocaine/prilocaine cream as an adjunct to lidocaine infiltration reduced the pain of infiltration and the pain associated with cryotherapy for the removal of genital warts. (J Am Acad Dermatol 1997; 37:96–100.)