To compare the topical and the pulpal anesthesia efficacy of liposomal and plain benzocaine formulations. Double-blinded, randomized crossover study. University ambulatory dental center. 30 ASA physical status I volunteers. Volunteers received, in three different sessions, topical application of liposome-encapsulated 10% benzocaine (LB10), 10% benzocaine gel (B10), and 20% benzocaine gel (B20) in the right maxillary canine mucobuccal fold. Pain associated with the needle insertion was rated by visual analog scale (VAS) and the duration of topical anesthesia was recorded. Pulpal anesthesia was evaluated using an electric pulp tester. VAS values (median, 1st - 3rd quartiles) were 17 cm (11 - 25), 14 cm (3 - 22), and 21 cm (9 - 21) for B10, LB10, and B20, respectively. No differences were noted among the groups (Friedman test; P = 0.58). Soft tissue anesthesia was also not different. The LB10 [10 (8 - 12) min] showed longer soft tissue anesthesia (Friedman test; P < 0.01) than the other agents [B10 = 8 (5 - 10) min, and B20 = 7 (6 - 9) min]. None of the topical benzocaine formulations tested induced pulpal anesthesia. The encapsulation of benzocaine into liposome increased the duration of soft tissue anesthesia. However, it did not induce pulpal anesthesia.22313-7