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Midurethral slings are commonly used to treat stress urinary incontinence. Pain control, however, may be a concern. Liposomal bupivacaine is a local anesthetic with slow release over 72 hours, demonstrated to lower pain scores and decrease narcotic use postoperatively.The purpose of this study was to examine the impact of liposomal bupivacaine on pain scores and narcotic consumption following retropubic midurethral sling placement.This randomized, placebo-controlled trial enrolled women undergoing retropubic midurethral sling procedures with or without concomitant anterior or urethrocele repair. Subjects were allocated to receive liposomal bupivacaine (intervention) or normal saline placebo injected into the trocar paths and vaginal incision at the conclusion of the procedure. At the time of drug administration, surgeons became unblinded, but did not collect outcome data. Participants remained blinded to treatment. Surgical procedures and perioperative care were standardized. The primary outcome was the visual analog scale pain score 4 hours after discharge home. Secondary outcomes included narcotic consumption, time to first bowel movement, and pain scores collected in the mornings and evenings until postoperative day 6. The morning pain item assessed “current level of pain”; the evening items queried “current level of pain,” “most intense pain today,” “average pain today with activity,” and “average pain today with rest.” Likert scales were used to measure satisfaction with pain control at 1- and 2-week postoperative intervals. Sample size calculation deemed 52 subjects per arm necessary to detect a mean difference of 10 mm on a 100-mm visual analog scale. To account for 10% drop out, 114 participants were needed.One hundred fourteen women were enrolled. After 5 exclusions, 109 cases were analyzed: 54 women received intervention, and 55 women received placebo. Mean participant age was 52 years, and mean body mass index was 30.4 kg/m2. Surgical and demographic characteristics were similar, except for a slightly higher body mass index in the placebo group (31.6 vs 29.2 kg/m2; P=.050), and fewer placebo arm subjects received midazolam during anesthesia induction (44 vs 52; P=.015). For the primary outcome, pain score (millimeter) 4 hours after discharge home was lower in the intervention group (3.5 vs 13.0 millimeters; P=.014). Pain scores were also lower for subjects receiving liposomal bupivacaine at other time points collected during the first three postoperative days. Furthermore, fewer subjects in the intervention group consumed narcotic medication on postoperative day 2 (12 vs 27; P=.006). There was no difference in satisfaction with pain control between groups. Side-effects experienced, rate of postoperative urinary retention, and time to first bowel movement were similar between groups. Finally, no serious adverse events were noted.Liposomal bupivacaine decreased postoperative pain scores following retropubic midurethral sling placement, though pain was low in both the intervention and placebo groups. Participants who received liposomal bupivacaine were less likely to use narcotics on postoperative day 2. For this common outpatient surgery, liposomal bupivacaine may be a beneficial addition. Given the cost of this intervention, however, future cost-effective analyses may be useful.