Background: We report here on the results, stratified by diagnosis, of a multicenter prospective study by surgeons unaffiliated with the design team of reverse shoulder arthroplasty (RSA) performed using a lateralized glenosphere. We hypothesized that outcomes would be comparable to those reported previously. Methods: A total of 245 patients underwent RSA for cuff tear arthropathy or glenohumeral arthritis with rotator cuff tear, rotator cuff tear with instability or escape and without glenohumeral arthritis, or failed shoulder arthroplasty. Clinical, radiographic, and self-assessed outcome measures were obtained preoperatively and at standardized time points postoperatively. At 2 years, 173 patients were available as 23 patients were deceased, 12 had undergone revision, and 37 were unavailable. Results: Range of motion and outcomes improved, irrespective of diagnosis. Active forward flexion, abduction, and external rotation improved (73-127 , 65-109 , and 24-37 , respectively, P <.0001 for all). Simple Shoulder Test (3.2-8.5) and American Shoulder and Elbow Surgeons scores (45-86) also improved. Scapular notching occurred in 13.3%; scapular spine/ acromial fractures in 6.5%. Patients undergoing revision shoulder arthroplasty improved more modestly. Conclusion: In this multicenter study, surgeons unaffiliated with the design team obtained clinical improvements comparable to those reported previously and that exceeded minimal clinically important differences for RSA. Improvements in external rotation and low scapular notching rates potentially relate to the lateralized design.