Background: Obesity increases the risk of type 2 diabetes and coronary artery disease (CAD). Because all 3 conditions may reduce quality of life, the extent to which obesity, diabetes, and CAD independently affect quality of life is uncertain. Methods: Patients with type 2 diabetes and documented CAD participating in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial at 45 clinical sites in the United States and Canada were studied in a cross-sectional analysis of baseline data. Quality of life was assessed with the Duke Activity Status Index, the energy/fatigue and health distress scales from the Medical Outcome Study, and overall self-rated health status. Results: Higher body mass index was significantly associated with worse scores on all 4 quality of life scales, even after adjustment for the severity of diabetes and CAD and other comorbid conditions. Use of insulin, angina, and current smoking were also associated with significantly lower quality of life on all 4 scales, independent of other factors. Conclusions: Obesity is associated with significantly reduced quality of life in patients with diabetes and CAD, independent of comorbid conditions. © 2010 Mosby, Inc. All rights reserved.