Background: A debate exists whether obesity is a risk factor for operative mortality after coronary artery bypass graft surgery (CABG). The contradictory findings in the literature may largely be attributable to the variety of methodological approaches used to model the association between body mass index (BMI) and post-CABG outcomes. This study aims to investigate this association, and to uncover possible explanations for the lack of consensus across prior studies. Methods: Data were prospectively collected on 80,792 patients who underwent a CABG procedure during a 14-year period at the 45 Department of Veterans Affairs cardiac surgery programs. Generalized additive models were used to estimate the relationship of BMI and outcomes after a CABG procedure. Results: We found that the relationship of BMI with post-CABG mortality and morbidity is U-shaped with the minimum risk located around a BMI of 30 kg/m2, indicating that patients classified as overweight have the lowest risk, and those in the lower end of the obese range do not have seriously elevated risk. This U-shape relationship is significantly nonlinear and robust to adjustment for other risk factors. Conclusions: This study demonstrates that BMI is an independent predictor of mortality and morbidity after CABG surgery. Previous studies that model BMI linearly or as categories cannot accurately capture this U-shaped relationship and are unlikely to find a significant contribution by including BMI. Further research is needed to determine the mechanisms of risk for patients with low and high BMI and whether interventions to modify BMI may improve patient outcomes. © 2007 The Society of Thoracic Surgeons.