Background: Following orthopedic surgery, patients frequently experience pain and discomfort. Multiple methods of regional anesthesia are available; however, the optimal technique to adequately manage pain while minimizing complications remains under investigation. This study aims to compare the complication rates and pain relief of single-injection, liposomal bupivacaine brachial plexus nerve block to a conventional, indwelling ropivacaine interscalene catheter (ISC) in patients undergoing arthroscopic shoulder surgery. We hypothesize that liposomal bupivacaine will have fewer patient complications with similar pain relief than an indwelling catheter. Methods: Patients undergoing arthroscopic shoulder surgery were prospectively assessed after randomization into either ropivacaine ISC or single-injection liposomal bupivacaine brachial plexus nerve block (LB) arms. All patients were discharged with 5 analgesics (acetaminophen, methocarbamol, gabapentin, acetylsalicylic acid, and oxycodone) for as-needed pain relief. Preoperatively, patient demographics and baseline Visual Analog Scale, Single Assessment Numeric Evaluation, American Shoulder and Elbow Surgeons, and Penn Shoulder Scores were obtained. For the first four days postoperatively, complication rates (nausea, dyspnea, anesthetic site discomfort and/or irritation and/or leakage, and self-reported concerns and complications), pain, medication usage, and sleep data were assessed by phone survey every 12 hours. The primary outcome was overall complication rate. At 12 weeks postoperatively, Visual Analog Scale, Single Assessment Numeric Evaluation, American Shoulder and Elbow Surgeons, and Penn scores were reassessed. Outcome scores were compared with Mann-Whitney U tests, and demographics were compared with chi-squared tests. Significance was set at P <.05. Results: A total of 63 individuals were allocated into ISC (N = 35) and in the LB arms (N = 28) for analysis. Demographics and preoperative patient-reported outcomes were not different between the arms. Patients in the LB arm experienced fewer (13.1%) overall complications than those in the ISC arm (29.8%) (P <.001), with patients in the ISC arm specifically reporting more anesthetic site discomfort (36.4% vs. 7.1%, P =.007), leakage (30.3% vs. 7.1%, P =.023), and ‘other,’ free-response complications (ISC: 21.2%; LB: 3.6%; P =.042). No differences were noted in pain, sleep, opioid use, or satisfaction between arms during the perioperative period. More nonopioid medications were consumed on average in the ISC (1.8 ± 1.4) than in the LB arm (1.4 ± 1.3) (P =.001), with greater reported use of acetylsalicylic acid (40.9% vs. 23.4% P <.001) and acetaminophen (69.5% vs. 59.6% P =.013). Patient-reported outcome scores did not differ between groups preoperatively or at 12 weeks. Discussion: Patients receiving liposomal bupivacaine experienced fewer complications than traditional ISCs after arthroscopic shoulder surgery. Analgesia, sleep, satisfaction, and functional scores were similar between the 2 groups.