OBJECTIVE: To investigate weight loss outcomes of semaglutide in a real-world setting, specifically in patients who have undergone metabolic/bariatric surgery (MBS). SUMMARY BACKGROUND DATA: Despite excellent weight loss for semaglutide in clinical trials, actual results may be limited due to factors such as costs, drug availability, insurance coverage, and adverse events. METHODS: A retrospective series of patients with obesity prescribed semaglutide at a large multidisciplinary weight management center in a tertiary academic institution. Primary endpoints were compliance and percentage total weight loss (%TWL) within 1 year of semaglutide prescription, with further evaluation of weight loss in those with previous history of MBS. RESULTS: The average [SD] %TWL at 1 year among all patients prescribed semaglutide was 8.8% [10.5]. Of 1,072 patients prescribed semaglutide, 199/1072 (18.6%) did not start semaglutide mainly due to access issues, and 268/1072 (25%) discontinued it within 1 year primarily due to patient factors and side effects. Among patients who completed 1 year of treatment, %TWL was 10.9% [9.8]. In those with history of MBS, %TWL was higher in patients who underwent Roux-en-Y Gastric Bypass (RYGB), but not sleeve gastrectomy, compared to no MBS history (13.6% [10.3] vs. 10.1% [9.6]; P=0.022). Furthermore, %TWL with semaglutide was less in those with BMI>40, than those with BMI<40. CONCLUSIONS: 1-year semaglutide compliance is low at 56.4%. 1-year TWL for all patients prescribed semaglutide was 8.8%, and 10.9% for those who took semaglutide for 1 complete year. Patients who underwent RYGB tended to lose more weight with semaglutide than naïve MBS patients.