156 patients scheduled for total shoulder arthroplasty were randomized to postoperative analgesia through either intraoperative periarticular injection of liposomal bupivacaine or preoperative single-shot interscalene brachial plexus block (ISBPB). Patients were assessed for perioperative morphine equivalent unit consumption and pain severity scores over the first 24 hours postoperatively. Intraoperative morphine equivalent unit consumption was significantly greater in the PAI liposomal bupivacaine group compared to the ISBPB group, while postoperative morphine consumption did not significantly differ between groups. Additionally, pain scores were significantly higher in the PAI liposomal bupivacaine group compared to the ISBPB group immediately after surgery and at 8 hours postoperatively, whereas pain scores at 24 hours were significantly lower in the PAI liposomal bupivacaine group compared to the ISBPB group.