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Background and Aims Regional anesthesia for proximal humeral orthopedic surgery facilitates awake or lightly sedated procedures, potentially mitigating risks associated with general anesthesia. Evidence supporting its comprehensive effectiveness, however, remains limited. We hypothesized that interscalene brachial plexus block with sedation, avoiding neuromuscular blockade, would improve intraoperative hemodynamic stability and other outcomes compared to general anesthesia with neuromuscular blockade.Methods This retrospective chart review analyzed patients undergoing open reduction and internal fixation or implant removal for proximal humeral fractures between April 2016 and January 2025. A matched-pair analysis, based on age, sex, surgery type, and ASA-PS classification, compared patients receiving interscalene brachial plexus block with appropriate sedation under spontaneous breathing (Group S) to those managed with positive pressure ventilation and neuromuscular blockade (Group P). The primary outcome measure was the ratio of the minimum mean arterial pressure (MAP) recorded during surgery to the baseline MAP at admission.Results Fifty-three matched pairs were analyzed The nadir MAP ratio was significantly higher in Group S (64.8 ± 16.6%) than in Group P (54.1 ± 10.7%) (Difference 10.7; 95% CI -16.0 to -5.3; p < 0.001), demonstrating improved hemodynamic stability. Intraoperative vasopressor use (phenylephrine and ephedrine) was significantly less frequent in Group S compared to Group P (Group S: 10 patients, Group P: 43 patients; p < 0.001). Recovery time, defined as the interval from the end of surgery to operating room discharge, was significantly shorter in Group S. Postoperative pain scores and time to cessation of supplemental oxygen administration did not differ significantly between groups.Conclusions Conclusion Interscalene brachial plexus block with neuromuscular blockade-free sedation may enhance intraoperative hemodynamic stability, reduce vasopressor requirements, and facilitate earlier operating room discharge following proximal humerus orthopedic surgery.