This study examined the effects of exercise and stress management training on clinical outcomes and medical expenditures over a 5-year follow-up period in 94 male patients with established coronary artery disease (CAD) and evidence of ambulatory or mental stress-induced myocardial ischemia. Patients were randomly assigned to 4 months of aerobic exercise 3 times per week or to a 1.5-hour weekly class on stress management; patients who lived too far from Duke to participate in the weekly treatments formed the usual care control group. Follow-up was performed at the end of treatment and annually thereafter for 5 years. Stress management was associated with a significant reduction in clinical CAD events relative to usual care over each of the first 2 years of follow-up and after 5 years. Economic analyses revealed that stress management was associated with lower medical costs than usual care and exercise in the first 2 years, and that the cumulative cost over 5 years was also lower for stress management relative to usual care. These results suggest that there may be clinical and economic benefit to offering the type of preventive stress management and exercise interventions provided to patients with myocardial ischemia. Moreover, these findings suggest that the financial benefits that accrue from an appropriately targeted intervention may be substantial and immediate.