BACKGROUND Liposomal lidocaine 4% (L.M.X.4 cream, Ferndale Laboratories Inc., Ferndale, MI, USA) has been proposed as a more rapidly acting topical anesthetic than the eutectic mixture of lidocaine 2.5% and prilocaine 2.5% (EMLA cream, AstraZeneca LP, Wilmington, DE, USA) for venipuncture and laser procedures. However, their anesthetic efficacy has not been previously compared for electrosurgical destruction of superficial skin lesions.OBJECTIVE To test the hypothesis that L.M.X.4 and EMLA differ in anesthetic efficacy when applied under occlusion for 30 minutes prior to electrodesiccation of papules of dermatosis papulosa nigra.METHODS Forty adults were randomly assigned to treatment with either agent for 30 minutes under Tegaderm. The study drug was administered for an additional 30 minutes if the electrodesiccation of the first few papules was too painful.RESULTS One subject treated with EMLA versus none treated with L.M.X.4 experienced complete anesthesia after a single 30-minute application. Nineteen of 20 (95%) subjects treated with EMLA versus 18 of 20 (90%) subjects treated with L.M.X.4 required only a single application (p = .49). Pain scores after the initial 30-minute application (scale: 0 = none to 10 = very severe) were EMLA 3.3 Ϯ 2.2 (mean Ϯ SD) versus L.M.X. 4 2.9 Ϯ 2.0 (p = .46). CONCLUSION EMLA and L.M.X.4 provide comparable levels of anesthesia after a single 30minute application under occlusion prior to electrodesiccation of superficial skin lesions.