The effect of obesity on long-term mortality after coronary artery bypass grafting (CABG) remains inconclusive, partly due to methodologic issues in previous studies. We examined the effect of obesity on long-term mortality (up to a 6-year follow-up) in adult patients with a body mass index (BMI) > or =18.5 kg/m2 who underwent CABG at Baylor University Medical Center (Dallas, Texas) between January 1998 and August 1999 (n = 1,209). Unadjusted analysis indicated a strong association between BMI and long-term mortality (p = 0.001), with a decreased risk of mortality associated with increasing BMI. After adjusting for factors shown to be confounders of this relation (age, diabetes mellitus, chronic obstructive lung disease, renal failure, ejection fraction, and left main disease), the estimated association was no longer significant (p = 0.425). In conclusion, the apparent survival benefit associated with higher BMI became nonsignificant when the relation between mortality and BMI was adjusted, first for age and then for diabetes mellitus, chronic obstructive lung disease, renal failure, ejection fraction, and left main disease. This relation was masked in the crude analysis primarily by the effect of age. Patients with a high BMI were typically younger than patients with a lower BMI, suggesting that physicians and surgeons may only recommend/perform CABG for patients with a high BMI with an otherwise lower risk profile.