This study examined the effect of the Ornish Program for Reversing Heart Disease and cardiac rehabilitation (CR) on psychosocial risk factors and quality of life in patients with confirmed coronary artery disease. Participants had previously undergone a revascularization procedure. The 84 patients self-selected to participate in the Ornish Program for Reversing Heart Disease (n = 507 28), CR (n = 28), or a control group (n = 28). Twelve psychosocial risk factors and quality of life variables were collected from all three groups at baseline, 3 months, and 6 months. At 3 and 6 months, Ornish group participants demonstrated significant improvements in all 12 outcome measures. The rehabilitation group improved in 7 of the 12, and the control group showed significant improvements in 6 of the variables. Intensive lifestyle modification programs significantly affect psychosocial risk factors and quality of life.