Background: Gastric bypass (GBP) is the most common operation performed in the United States for morbid obesity. However, weight loss is poor in 10% to 15% of patients. We sought to determine the independent factors associated with poor weight loss after GBP. Design: Prospective cohort study.. We examined demographic, operative, and follow-up data by means of multivariate analysis. Variables investigated were age, sex, race, marital and insurance status, initial weight and body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared), comorbidities (diabetes mellitus, hypertension, joint disease, sleep apnea, byperlipidemia, and psychiatric disease), laparoscopic vs; open surgery, gastric pouch area, gastrojejunostomy technique, and alimentary limb length. Setting: University tertiary referral center. Patients: All patients at our institution who underwent. GBP from January 1, 2003, through July 30, 2006. Main Outcome Measures: Weight loss at 12 months. defined as poor (<= 40% excess weight loss) or good (>40% excess weight loss). Results: Follow-up data at 12 months were available for 310 of the 361 patients (85.9%) undergoing GBP during the study period. Mean preoperative BMI was 52 (range, 36-108). Mean BMI and excess weight loss at follow-up were 34 (range, 17-74) and 60% (range, 8%-117%), respectively. Thirty-eight patients (12.3%) had poor weight loss. Of the 4 variables associated with poor weight loss in the univariate analysis (greater initial weight, diabetes, open approach, and larger pouch size), only diabetes (odds ratio, 3.09; 95% confidence interval, 1.35-7.09 [P = .0071) and larger pouch size (odds ratio, 2.77; 95% confidence interval, 1.81-4.22 [P < .0011) remained after the multivariate analysis. Conclusions: Gastric bypass results in substantial weight loss in most patients. Diabetes and larger pouch size are independently associated with poor weight loss after GBP.