Study Objective: To compare the safety and efficacy of remifentanil and propofol as adjuncts to regional anesthesia in patients undergoing orthopedic or urogenital surgery. Design: Prospective, randomized study. Setting: Multicenter university hospitals. Patients: 107 ASA physical status I, II, and III adult patients who underwent orthopedic or urogenital surgery with axillary, ankle, or spinal block. Interventions: Patients were randomized to receive either an infusion of remifentanil 0.2 μg/kg/min or propofol 100 μg/kg/min 5 minutes before nerve block placement. The infusions were decreased by 50% on block completion, increased by 50% for patient discomfort, and decreased by 50% for hypoventilation (<8 breaths/min) or hemodynamic instability. Measurements and Main Results: Pain, discomfort, anxiety, and sedation were assessed by both patient and investigator. Vital signs and adverse events were recorded. Fewer patients in the remifentanil group experienced pain during block placement (6%), and were oversedated (7%) than patients in the propofol group (23% and 26%, respectively; p < 0.05). Hypoventilation during and after block placement (21% and 25%, respectively) and nausea and vomiting during and after block placement (60% and 21%, respectively) were more common in the remifentanil group than in the propofol group (0% and 3%; 17% and 6%, respectively; p < 0.05). The incidence of hypoventilation in remifentanil-treated patients was higher in patients over 65 years of age ( p < 0.05), but was transient, resolving within minutes of discontinuing the infusion. Conclusions: At the doses studied, remifentanil was more effective than propofol in minimizing pain without producing excessive sedation. Remifentanil was associated with more transient respiratory depression and short-term nausea. Our findings indicate that the initial remifentanil rate should be 0.1 μg/kg/min (50% lower than the study's initial rate) and should be further decreased an additional 50% in the elderly to minimize adverse effects.