BACKGROUND: This study investigated the effect of topical analgesic effects of a liposome encapsulated mixture of local anesthetics (lipo-MLA) compared with EMLA. METHODS: 3% lipo-MLA (0.5% tetracaine base, 2.5% lidocaine base) and 5% lipo-MLA (1% tetracaine base, 4% lidocaine base) were encapsulated into liposomal vesicles made with egg yolk phosphatidylcholine, cholesterol and phosphatidyldioleoyl. 3% lipo-MLA and EMLA were applied to volunteers' forearms bilaterally with and without an occlusive dressing. The topical anesthetic effects of the lipo-MLA and EMLA as a control were evaluated by the pinprick test in 28 adult volunteers after 60 minutes of application. The analgesic influence of the concentration of local anesthetics was also compared with 3% and 5% lipo-MLA under a non-occlusive dressing. RESULTS: Analgesic effects of the 3% lipo-MLA were similar with EMLA under an occlusive dressing for 60 minutes. In addition, analgesic effects of the 3% lipo-MLA under a non-occlusive dressing were more potent than EMLA. Lipo-MLA under a non-occlusive dressing showed more potent analgesic effect than lipo-MLA under an occlusive dressing. 5% lipo-MLA was more potent than 3% lipo-MLA under a non-occlusive dressing. CONCLUSIONS: Lipo-MLA has more potent analgesic effects than EMLA without an occlusive dressing and 5% lipo-MLA is more potent than 3% lipo-MLA. Therefore, lipo-MLA appeared to be an improved topical analgesic formulation which provides a more potent and convenient topical application.