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Background: Anatomic total shoulder arthroplasty with a nonspherical humeral head and inlay glenoid replacement has been introduced in the past; however, clinical evidence remains limited. We hypothesized that patients with advanced glenohumeral arthritis demonstrate significant improvements in pain and function. Methods: Prospective patient-reported outcomes (PROs) included the American Shoulder and Elbow Surgeons score, a pain visual analog scale, and satisfaction. Range of motion was compared to the preoperative status. A sensitivity analysis examined responder rates and compared them to literature thresholds using the minimal clinically important difference and substantial clinical benefit. The preoperative glenoid morphology was determined using the Walsh classification. Zone-specific periprosthetic radiolucent lines were quantified at the last follow-up. Results: Thirty-nine shoulders in 36 patients (3 bilateral) with a mean age of 65.9 years (26 males, 13 females) and a mean follow-up of 41.0 months were included. Ninety-three percent had grade III osteoarthritis, and 7% grade II. The glenoid Walsh classification included A1 (25%), A2 (25%), B1 (22%), B2 (25%), and C (3%). All PROs improved significantly (P