ABSTRACT Background Roux-en-Y gastric bypass (RYGB) has been reported to remit type 2 diabetes and to reduce rates of cardiovascular disease by lipid profile improvement. However, there are no longitudinal data that address lipid profiles in different ethnic groups following bariatric surgery. Method Retrospective chart reviews were conducted for 913 consecutive obese patients undergoing gastric restrictive surgery in Boston Medical Center from 2004 to 2010. For these analyses, we included 825 patients consisting of 166 African Americans, 505 Caucasian Americans and 154 Hispanic Americans with 2 years of follow-up data. Mean levels for lipids and glycemic control were compared with ANOVA and longitudinal mixed linear modeling Results After RYGB, all obese subjects in three racial groups showed improvement in glycemic control and lipid profile over two years follow up. Multivariate analysis further demonstrated that two years after RYGB, African Americans showed significantly less improvement in HbA1C compared with white obese patients and Hispanic Americans (p=.003 and p=.004, respectively). Lipid profiles appeared to be less favorable in whites than in African Americans. When other factors significantly affecting lipid levels were adjusted for in multivariate models, African Americans consistently maintained the lowest TG concentrations and highest HDL of three racial groups while the least favorable levels were observed in Caucasian Americans, even after adjusting for percent of maximal weight loss. For total cholesterol and LDL level, obese Hispanic American patients significantly improved in their first six months after operation. However, Hispanic Americans having a higher level than African Americans (p=.0021) and Caucasians (p=0.3498) at 24 months after surgery. Conclusion These significant differences in glycemic control and lipid profiles after RYGB in this ethnically-diverse group of obese patients suggest that it is critical to consider race/ethnicity in designing appropriate treatment modalities for obese patients undergoing gastric bypass surgery.