Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Animal studies have shown that liposome encapsulation increases prilocaine anesthetic efficacy. This randomized, blind, crossover, three-period study evaluated the anesthetic efficacy of liposome-encapsulated 3% prilocaine, compared to 3% plain prilocaine and 3% prilocaine with 0.03IU/mL felypressin, after a 1.8-mL infiltration in the buccal sulcus of the maxillary right canine, in 32 volunteers. Anesthesia success, onset, and duration of pulpal and gingival anesthesia in the lateral incisor, and canine and first premolar were evaluated. Injection pain was assessed by a visual analog scale (VAS). Results were submitted to Kruskal-Wallis (onset and duration of pulpal anesthesia), Tukey (VAS), Friedman (duration of gingival anesthesia), and log-rank and McNemar tests (anesthesia success) (a = 5%). Liposomal prilocaine did not differ from plain prilocaine (P > 0.05), but presented lower anesthesia success and duration for canine, premolar, and gingival anesthesia (P < 0.05) than prilocaine with felypressin. Liposomal prilocaine did not differ from the other formulations concerning onset and anesthesia success for the lateral incisor (p > 0.05); plain prilocaine presented lower success rates and slower onset of anesthesia for this tooth, in comparison to prilocaine with felypressin (P < 0.05). No differences were observed among the formulations in relation to duration of anesthesia for lateral incisor, VAS scores, and onset of gingival and pulpal anesthesia for the canine and premolar (P > 0.05). In conclusion, liposomal prilocaine presents similar anesthetic efficacy in relation to plain prilocaine and lower efficacy, in comparison to prilocaine with felypressin in maxillary infiltration. Prilocaine does not seem to benefit from liposomal encapsulation.2118187Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP [06/00121-9]CNPq [131843/2008-7]