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Background: Early designs of reverse shoulder arthroplasty components for the treatment of glenohumeral arthritis associated with severe rotator cuff deficiency in some cases have been associated with mechanical failure. The purpose of this study was to perform a prospective outcomes study of reverse shoulder arthroplasty performed with use of 5.0-mm peripheral locking screws for baseplate fixation and a lateralized center of rotation for the treatment of a rotator cuff deficiency.Methods: From February 2004 to March 2005, 112 patients (114 shoulders) were treated with a reverse shoulder arthroplasty as part of a United States Food and Drug Administration Investigational Device Exemption study. Ninety-four patients (ninety-six shoulders) were available for a minimum follow-up of two years. Of the ninety-six shoulders, thirty-seven had a primary rotator cuff deficiency, thirty-three had a previous rotator cuff operation, twenty-three had a previous arthroplasty, and three had a proximal humeral nonunion. The patients were prospectively followed clinically (the American Shoulder and Elbow Surgeons [ASES] score, the Simple Shoulder Test [SST], and self-reported satisfaction) and radiographically (mechanical failure, loosening, and notching). Patients were videotaped while performing a standard active range-of-motion protocol before and after treatment. These videos were then analyzed in a blinded fashion by three independent observers using a digital goniometer.Results: At two years, the average total ASES scores had improved from 30 preoperatively to 77.6; the average ASES pain scores, from 15 to 41.6; and the average SST scores, from 1.8 to 6.8 (p < 0.0001 for all). Blinded analysis of range of motion showed that average abduction improved from 61° preoperatively to 109.5° (p < 0.0001); average flexion, from 63.5° to 118° (p < 0.0001); and average external rotation, from 13.4° to 28.2° (p < 0.0001). The patients rated the outcome as excellent in fifty-three shoulders (55%), good in twenty-six (27%), satisfactory in eleven (12%), and unsatisfactory in six (6%). There was no evidence of mechanical failure of the baseplate or scapular notching in any of the patients. Six of the ninety-four patients in this study had a complication.Conclusions: Recent advances in reverse shoulder arthroplasty have allowed for improvement in patient outcomes while minimizing early mechanical failure and scapular notching and decreasing the overall complication rate at short-term follow-up.Level of Evidence: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence.