Axillary pain is common after arthroscopic shoulder surgery with an open subpectoral biceps tenodesis. We hypothesized that adding a pectoral nerve block II (Pecs II) to an interscalene block (ISB) would improve postoperative analgesia in this surgical population.Forty patients were enrolled in this prospective, randomized, observer and patient-blinded, single-institution trial. All 40 patients received a single-injection ISB with 20 mL of 0.25% bupivacaine with 1:400,000 epinephrine and 1:600,000 clonidine. The intervention arm (ISB + Pecs II) consisted of 20 patients who also received a Pecs II block using 30 mL of 0.25% bupivacaine with 1:400,000 epinephrine and 1:600,000 clonidine. The 20 control group patients (ISB) received a sham Pecs II block. The primary outcome was postoperative pain scores at 6 hours using the numeric rating scale (NRS; range, 0-10) and was analyzed using the Mann-Whitney U test. Secondary outcomes included the presence of axillary pain at 6 hours, the need for postanesthesia care unit (PACU) opioids, PACU length of stay (LOS) (minutes), NRS pain scores at 24 hours, cumulative opioid usage postdischarge through 24 hours, the presence of nausea or vomiting during the first 24 hours, and Pecs II block duration (in hours, based on time to onset of axillary pain). Data were analyzed using a modified intention-to-treat (ITT) methodology.Pain scores (NRS, 0-10) at 6 hours differed significantly between groups: ISB 3.0 (0.25-5.0) (1.7-4.3) versus ISB + Pecs II 0.0 (0-2.0) (0.0-1.1) (median [IQR] [95% CI]); P = .026. Hodges-Lehmann estimator of the difference was 2.0 (95% CI, 0.0-4.0). Fewer patients in the ISB + Pecs II group reported axillary pain at 6 hours and fewer required opioids in the PACU. There were no differences in any of the remaining secondary outcomes.The addition of a Pecs II block to an ISB for patients undergoing arthroscopic shoulder surgery with an open subpectoral biceps tenodesis significantly improved postoperative analgesia and reduced the need for opioids in the PACU.