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STUDY OBJECTIVE To study the effects of liposomal bupivacaine (LB) compared with bupivacaine hydrochloride with lidocaine on postoperative day 1 pain scores. DESIGN A randomized controlled trial (Canadian Task Force classification 1). SETTING An academic medical center within the department of female pelvic medicine and reconstructive surgery. PATIENTS Fifty-seven patients undergoing midurethral sling placement by a fellowship-trained urogynecologic surgeon and a fellow in female pelvic medicine and reconstructive surgery. INTERVENTIONS Fifty-seven patients were enrolled to participate in this study. There were 24 patients randomized to receive liposomal bupivacaine and 33 to receive a mixture of bupivacaine and lidocaine during the placement of a retropubic midurethral sling. MEASUREMENTS AND MAIN RESULTS Patients were given a diary of pain scales and asked to record their level of pain using the provided visual analog scale scored on a 100-mm Likert scale. Patients recorded their pain 4 hours after hospital discharge and on the night of surgery and their most intense pain each day thereafter for 7 days postoperatively. In addition, patients recorded total opioid and nonsteroidal anti-inflammatory drug consumption daily for 1 week postoperatively. Finally, the quality of recovery was assessed using the Quality of Recovery-15 (QoR-15) questionnaire scores. The median pain score in the experimental group was 20 mm (range, 0-80 mm) versus 30 mm (range, 0-60 mm) in the comparative group (p = .046). The postoperative day 1 QoR-15 scores were significantly lower in the LB group (124 [range, 54-150] vs 144 [range, 68-150], p = .007). There were no significant differences in opioid and nonsteroidal anti-inflammatory drug consumption, the remaining pain scores, or postoperative day 7 QoR-15 scores. CONCLUSION The results suggest the use of liposomal bupivacaine during retropubic midurethral sling placement does not provide a clinically significant difference in postoperative day 1 pain scores when compared with immediate-acting bupivacaine hydrochloride and lidocaine.