Obesity is strongly associated with coronary artery disease (CAD) and may be an independent risk factor; however, limited data are available on obesity intervention in patients with CAD. We studied 588 consecutive patients, including 235 (40%) who were obese by body mass index criteria (body mass index > or = 27.3 kg/m2 in women and > or = 27.8 kg/m2 in men) before and after out-patient phase II cardiac rehabilitation to determine the effects of this therapy and weight reduction on exercise capacity, CAD risk factors, behavioral characteristics, and quality of life in obese patients with CAD. At baseline, obese patients were younger (p < 0.0001) and had more systemic hypertension (p < 0.01), and diabetes mellitus (p < 0.05) and higher percent body fat (p < 0.0001), total cholesterol (p = 0.02), triglycerides (p < 0.0001), fasting glucose (p = 0.04), and low-density lipoprotein (LDL)-high-density lipoprotein (HDL) cholesterol (p < 0.0001), but had lower HDL cholesterol (p < 0.01) and exercise capacity (p = 0.07) than patients not classified as obese. After rehabilitation, obese patients had significant improvements in body mass index (-2%; p < 0.0001), percent body fat (-5%; p < 0.0001), exercise capacity (+27%; p < 0.0001), HDL cholesterol (+4%; p < 0.01), LDL/HDL ratio (-6%; p < 0.01), as well as scores for anxiety (p < 0.0001), depression (p < 0.01), somatization (p < 0.0001) and quality of life (p < 0.0001); nonobese patients, however, had significantly greater improvements in exercise capacity (+39% vs +27%; p < 0.001). In a subgroup of 45 obese patients with > or = 5% weight reduction, improvements in exercise capacity (p < 0.001), total cholesterol (p = 0.03), triglycerides (p < 0.01), HDL cholesterol (p < 0.001), LDL cholesterol (p = 0.02), and LDL/HDL ratio (p < 0.0001) were greater than improvements in 81 obese patients who did not lose weight. These data indicate that greater emphasis on more successful weight reduction programs is needed to further enhance CAD risk reduction in the 40% CAD patients with obesity.