Although Roux-en-Y gastric bypass surgery (RYGBP) is safe and effective at achieving weight loss in the majority of severely obese patients, a subset fails to achieve expected weight loss outcomes. Factors associated with poor weight loss are not well defined. Patients undergoing open RYGBP using a standardized surgical technique and clinical pathway by a single surgeon at a dedicated bariatric center were reviewed. Suboptimal weight loss was defined as failure to lose at least 40% excess body weight by 12 months postoperatively. Of 555 consecutive patients who underwent RYGBP from 1999 to 2004, a 12-month follow-up was available for the 495 (89%). Suboptimal weight loss occurred in 55 (11%) and was associated on unadjusted bivariate analysis with increased body mass index (BMI; p = 0.0002), diabetes mellitus (p = 0.0002), Medicaid insurance (p = 0.04), and male sex (p = 0.01). On adjusted multivariate analysis, increased BMI (p = 0.003), diabetes (p = 0.002), and male gender (p = 0.04) were associated with suboptimal weight loss, but type of insurance (p = 0.11) was not. Medicaid patients were younger (p = 0.01) and had higher BMI (p = 0.0002). Suboptimal weight loss after RYGBP appears to be associated with greater BMI, male sex, and diabetes but not type of insurance. This study may help identify patients who could benefit from increased perioperative education and counseling or selection of procedures with greater malabsorption.