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The interscalene nerve block provides analgesia for shoulder surgery, but is associated with diaphragm paralysis. One solution may be performing brachial plexus blocks more distally. This noninferiority study evaluated analgesia for blocks at the supraclavicular and anterior suprascapular levels, comparing them individually to the interscalene approach.One hundred-eighty-nine subjects undergoing arthroscopic shoulder surgery were recruited to this double-blind trial and randomized to interscalene, supraclavicular, or anterior suprascapular block using 15 ml, 0.5% ropivacaine. The primary outcome was numeric rating scale pain scores analyzed using noninferiority testing. The predefined noninferiority margin was one point on the 11-point pain scale. Secondary outcomes included opioid consumption and pulmonary assessments.All subjects completed the study through the primary outcome analysis. Mean pain after surgery was: interscalene = 1.9 (95% CI, 1.3 to 2.5), supraclavicular = 2.3 (1.7 to 2.9), suprascapular = 2.0 (1.4 to 2.6). The primary outcome, mean pain score difference of supraclavicular–interscalene was 0.4 (–0.4 to 1.2; P = 0.088 for noninferiority) and of suprascapular–interscalene was 0.1 (–0.7 to 0.9; P = 0.012 for noninferiority). Secondary outcomes showed similar opioid consumption with better preservation of vital capacity in the anterior suprascapular group (90% baseline [P < 0.001]) and the supraclavicular group (76% [P = 0.002]) when compared to the interscalene group (67%).The anterior suprascapular block, but not the supraclavicular, provides noninferior analgesia compared to the interscalene approach for major arthroscopic shoulder surgery. Pulmonary function is best preserved with the anterior suprascapular nerve block.