OBJECTIVE To explore the influence of liposomes on the pharmacodynamic action of bupivacaine and to determine whether postsurgical analgesic advantages can be obtained from epidural delivery of liposomal bupivacaine compared with the current formulation. METHODS Open, nonrandomized study. METHODS Physiopathology laboratory, general operating theaters, and intensive care units of Reine Fabiola Hospital and Institut Médical de Traumatologie et Revalidation. METHODS 26 ASA physical status II and III patients who had undergone major surgery (abdominal, vascular, urologic, thoracic, orthopedic). METHODS After completion of the operation, the patients were divided into 2 groups to receive 1 of 2 bupivacaine preparations epidurally for postsurgical pain: Group 1 (n = 12) received plain 0.5% bupivacaine with 1:200,000 epinephrine; Group 2 (n = 14) received liposomal 0.5% bupivacaine. RESULTS The following observations were made: onset and quality of analgesia, quality of motor block according to the Bromage scale, and sympathetic block. Onset time of sensory block averaged 15 minutes in both groups. Pain relief durations were 3.2 +/- 0.4 hours with plain bupivacaine and 6.25 +/- 1.13 hours with the liposomal preparation (p < 0.05). In the liposomal bupivacaine group, no motor block was recorded. Low sympathetic block occurred in all patients. Analgesia in a subset of patients following abdominal aortic surgery increased from 2.4 +/- 0.35 hours to 10.6 +/- 1.4 hours by encapsulation of bupivacaine (p < 0.01). There was no neurotoxicity or cardiotoxicity. CONCLUSIONS The liposomal formulation of bupivacaine increased duration of analgesia without motor block or adverse side effects.