57 patients scheduled for total shoulder arthroplasty or reverse total shoulder arthroplasty were randomized to postoperative analgesia with either local anesthesia via infiltration of liposomal bupivacaine into surrounding tissues, or with regional anesthesia via an interscalene brachial plexus block. The purpose of this study was to compare analgesic efficacy between groups. The primary outcome was pain score on a visual analog scale. For the first 8 hours after surgery, pain scores were significantly higher in the liposomal bupivacaine group compared to the interscalene block group. Thereafter, differences between groups were not significant.