Although anatomic total shoulder arthroplasty (TSA) successfully improves pain and function, not all patients improve clinically. This study was conducted to determine patient-related factors for failure to achieve improvement after primary TSA for osteoarthritis at 2 years postoperatively. This prospective study reviewed an institutional shoulder registry for consecutive patients who underwent primary TSA for osteoarthritis from 2007 to 2013 with baseline and 2-year postoperative American Shoulder and Elbow Surgeons (ASES) Standardized Shoulder Assessment Form scores. A failed outcome was defined as (1) a failure to reach the ASES minimal clinically important difference of 16.1 points or (2) revision surgery within 2 years of the index procedure, or both. Univariate and multivariable analyses of clinical and demographic patient factors were performed using logistic regression. Of 459 arthroplasties that met inclusion criteria, 411 were deemed successful by the aforementioned criteria, and 48 (10.5%) failed to achieve a desirable outcome. Clinical risk factors associated with failure included previous surgery to the shoulder (P = .047), presence of a torn rotator cuff (P = .025), and presence of diabetes (P = .036), after adjusting for age, sex, race, and body mass index. A higher preoperative ASES score at baseline was associated with failure (P < .001). Previous shoulder surgery, a rotator cuff tear requiring repair during TSA, presence of diabetes, surgery on the nondominant arm, and a higher baseline ASES score were associated with a higher risk of failing to achieve improvement after anatomic TSA.