BACKGROUND Few long-term or controlled studies of bariatric surgery have been conducted to date. We report the 12-year follow-up results of an observational, prospective study of Roux-en-Y gastric bypass that was conducted in the United States. METHODS A total of 1156 patients with severe obesity comprised three groups: 418 patients who sought and underwent Roux-en-Y gastric bypass (surgery group), 417 patients who sought but did not undergo surgery (primarily for insurance reasons) (non-surgery group 1), and 321 patients who did not seek surgery (nonsurgery group 2). We performed clinical examinations at baseline and at 2 years, 6 years, and 12 years to ascertain the presence of type 2 diabetes, hypertension, and dyslipidemia. RESULTS The follow-up rate exceeded 90% at 12 years. The adjusted mean change from baseline in body weight in the surgery group was −45.0 kg (95% confidence interval [CI], −47.2 to −42.9; mean percent change, −35.0) at 2 years, −36.3 kg (95% CI, −39.0 to −33.5; mean percent change, −28.0) at 6 years, and −35.0 kg (95% CI, −38.4 to −31.7; mean percent change, −26.9) at 12 years; the mean change at 12 years in nonsurgery group 1 was −2.9 kg (95% CI, −6.9 to 1.0; mean percent change, −2.0), and the mean change at 12 years in nonsurgery group 2 was 0 kg (95% CI, −3.5 to 3.5; mean percent change, −0.9). Among the patients in the surgery group who had type 2 diabetes at baseline, type 2 diabetes remitted in 66 of 88 patients (75%) at 2 years, in 54 of 87 patients (62%) at 6 years, and in 43 of 84 patients (51%) at 12 years. The odds ratio for the incidence of type 2 diabetes at 12 years was 0.08 (95% CI, 0.03 to 0.24) for the surgery group versus nonsurgery group 1 and 0.09 (95% CI, 0.03 to 0.29) for the surgery group versus nonsurgery group 2 (P<0.001 for both comparisons). The surgery group had higher remission rates and lower incidence rates of hypertension and dyslipidemia than did nonsurgery group 1 (P<0.05 for all comparisons). CONCLUSIONS This study showed long-term durability of weight loss and effective remission and prevention of type 2 diabetes, hypertension, and dyslipidemia after Roux-en-Y gastric bypass. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.)