BACKGROUND:The analgesic effect of adding liposomal bupivacaine to standard bupivacaine in supraclavicular brachial plexus block is not known. The authors hypothesized that addition of liposomal bupivacaine would reduce acute postoperative pain compared to standard bupivacaine alone. METHODS:A randomized controlled trial was conducted. Patients and outcome assessors were blinded. Eighty patients undergoing distal radial fracture fixation during regional anesthesia with supraclavicular brachial plexus block were randomized into two groups. The liposomal bupivacaine group received 10 ml 0.5% plain bupivacaine immediately followed by 10 ml 1.33% liposomal bupivacaine (n = 40). The standard bupivacaine group received 20 ml 0.5% plain bupivacaine (n = 40). The primary outcome was weighted area under curve (AUC) numerical rating scale pain score at rest during the first 48 h after surgery. Secondary outcomes included weighted AUC scores for pain with movement, overall benefit with analgesia score, and other functional scores. RESULTS:For the primary outcome, the liposomal bupivacaine group was associated with statistically significantly lower weighted AUC pain score at rest (0.6 vs. 1.4; P < 0.001) in the first 48 h. Of the secondary outcomes, no difference between treatment groups reached statistical significance with the exception of weighted AUC score for pain with movement (2.3 vs. 3.7; adjusted P < 0.001) and overall benefit with analgesia score (1.1 vs. 1.7; adjusted P = 0.020) in the first 48 h, as well as numerical rating scale pain score at rest (0.5 vs. 1.9; adjusted P < 0.001) and with movement (2.7 vs. 4.9; adjusted P < 0.001) on postoperative day 1. Differences in numerical rating scale pain scores on postoperative days 2, 3, and 4 did not reach the level of statistical significance. There were no statistically significant differences in sensory function. CONCLUSIONS:Liposomal bupivacaine given via supraclavicular brachial plexus block reduced pain at rest in the early postoperative period. EDITOR’S PERSPECTIVE: