Multimodal pain regimens in total shoulder arthroplasty (TSA) now include regional anesthetic techniques. Historically, regional anesthesia for extended postoperative pain control in TSA was administered using a continuous interscalene catheter (CIC). Liposomal bupivacaine (LB) is used for its potential for similar pain control and fewer complications compared with indwelling catheters. We evaluated the efficacy of interscalene LB compared with a CIC in postoperative pain control for patients undergoing TSA. This was a retrospective cohort study at a tertiary-care academic medical center including consecutive patients undergoing primary anatomic or reverse TSA from 2016 to 2020 who received either single-shot LB or a CIC for perioperative pain control. Perioperative and outcome variables were collected. The primary outcome was postoperative pain control, whereas the secondary outcome was health care utilization. The study included 565 patients, with 242 in the CIC cohort and 323 in the LB cohort. Demographic characteristics including sex (P=.99) and race (P=.81) were similar between the cohorts. The LB cohort had significantly lower mean pain scores at 24 hours (3 vs. 2, P<.001) and 36 hours (3 vs. 2, P<.001) postoperatively. The CIC cohort showed a higher percentage of patients experiencing a pain score of 9 or 10 postoperatively (29% vs. 17%, P=.001), whereas the LB cohort had a significantly greater proportion of opioid-free patients (32% vs. 10%, P<.001). Additionally, a greater proportion of CIC patients required opioid escalation to patient-controlled analgesia (7% vs. 2%, P=.002). The CIC cohort experienced a greater length of stay (2.3 days vs. 2.1 days, P=.01) and more 30-day emergency department visits (5% vs. 2%, P=.038). LB demonstrated lower mean pain scores at 24 and 36 hours postoperatively and lower rates of severe postoperative pain. Additionally, LB patients showed significantly higher rates of opioid-free pain regimens. These results suggest that as part of a multimodal pain regimen in primary shoulder arthroplasty, LB may provide greater reductions in pain and opioid use when compared with CICs.