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Our study identified several behaviors (eg, more sedentary time, eating fast food, binge eating, eating continuously, not weighing oneself regularly) and characteristics (eg, younger age, depressive symptoms) independently associated with greater weight regain after Roux-en-Y gastric bypass, which inform patient care to improve long-term weight loss maintenance.To identify patient behaviors and characteristics related to weight regain after Roux-en-Y gastric bypass surgery (RYGB).There is considerable variation in the magnitude of weight regain after RYGB, highlighting the importance of patient-level factors.A prospective cohort study of adults who underwent bariatric surgery in 6 US cities between 2006 and 2009 included presurgery, and 6-month and annual assessments for up to 7 years. Of 1573 eligible participants, 1278 (81%) with adequate follow-up were included (80% female, median age 46 years, median body mass index 46 kg/m2). Percentage of maximum weight lost was calculated each year after weight nadir.Weight was measured a median of 8 (25th–75th percentile, 7–8) times over a median of 6.6 (25th–75th percentile, 5.9–7.0) years. β coefficients, that is, the mean weight regain, compared with the reference, and 95% confidence interval, are reported. Postsurgery behaviors independently associated with weight regain were: sedentary time [2.9% (1.2–4.7), for highest vs lowest quartile], eating fast food [0.5% (0.2–0.7) per meal/wk], eating when feeling full [2.9% (1.2–4.5)], eating continuously [1.6% (0.1–3.1)], binge eating and loss-of-control eating [8.0% (5.1–11.0) for binge eating; 1.6 (−0.1 to 3.3) for loss of control, vs neither], and weighing oneself Several behaviors and characteristics associated with greater weight regain were identified, which inform integrated healthcare approaches to patient care and identify high-risk patients to improve long-term weight loss maintenance after RYGB.