Background The American Shoulder and Elbow Surgeons (ASES) questionnaire was developed to provide a standardized method for evaluating shoulder function. Previous studies have determined the clinical responsiveness of this outcome measure for heterogenous populations or patients with nonoperatively treated rotator cuff disease. Currently, to our knowledge, no studies exist that establish the clinically relevant change in the ASES score after shoulder arthroplasty. Questions/purposes We asked: (1) What are the minimal clinically important difference (MCID) and substantial clinical benefit (SCB) for the ASES score after primary and reverse shoulder arthroplasties? (2) Are the MCID and SCB for the ASES score different between primary and reverse shoulder arthroplasties? (3) What patient-related factors are associated with achieving the MCID and SCB after total shoulder arthroplasty and reverse shoulder arthroplasty? Methods A longitudinally maintained institutional shoulder arthroplasty registry was retrospectively queried for patients who underwent primary shoulder arthroplasty, including anatomic or reverse total shoulder arthroplasty from 2007 to 2013, with a minimum 2-year followup. Seven hundred ninety-four patients were identified and eligible; 304 of these patients did not have 2 years of followup or complete datasets, resulting in a study cohort of 490 patients (62% of the 794 potentially eligible). The MCID and SCB of the ASES score for these patients was calculated using an anchor-based method, using four different anchors measuring satisfaction with work, activities, overall, and activity from the SF-36. The MCID (anchored to somewhat satisfied) and SCB (very satisfied) of the ASES score were calculated for the entire cohort and stratified by arthroplasty type. Multivariate logistic regression of patient-related factors that influence the MCID and SCB achievement was performed. Results The MCID for all patients combined ranged from 6.3 to 13.5; for the overall satisfaction anchor, the MCID was 13.5 ± 4.5 (95% CI, 4.8-22.3). The SCB for the overall cohort ranged from 12.0 to 36.6; for the overall satisfaction anchor, the SCB was 36.6 ± 3.8 (95% CI, 29.1-44.1). There were no differences in the MCID of the ASES score between anatomic and reverse shoulder arthroplasty for any of the anchors (p = 0.159-0.992) or the SCB for any of the anchors (p = 0.467-0.977). CombiningOne of the authors certifies that he (LVG), or a member of his immediate family, has or may receive payments or benefits, during the study period, an amount of USD 10,000-USD 100,000 from Biomet, Inc (Warsaw, IN, USA). One of the authors certifies that he, (DMD) or a member of his immediate family, has or may receive payments or benefits, during the study period, an amount of USD 10,000-USD 100,000 from Biomet, Inc (Warsaw, IN, USA). All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research 1 editors and board members are on file with the publication and can be viewed on request. Each author certif...