Previous studies of patients with stable coronary artery disease have demonstrated that decreases in the left ventricular ejection fraction (LVEF) during acute mental stress are predictive of adverse clinical outcomes. The aim of the present study was to examine the prospective relation of mental stress on clinical outcomes in a sample of 138 patients with stable coronary artery disease. Patients underwent mental stress testing and were followed for a median of 5.9 years to assess the occurrence of the combined end point of myocardial infarction or all-cause mortality. There were 32 events (17 nonfatal myocardial infarctions and 15 deaths) over the follow-up period. Of the 26 patients who exhibited myocardial ischemia during mental stress testing, 11 (42%) sustained subsequent clinical events, compared to 21 of the 112 patients (19%) who showed no mental stress–induced ischemia. LVEF change during mental stress was also related to the clinical events in a graded, continuous fashion, with each 4% decrease from the LVEF at rest associated with an adjusted hazard ratio of 1.7, (95% confidence interval 1.1 to 2.6, p = 0.011). In conclusion, reductions in the LVEF during mental stress are prospectively associated with adverse clinical outcomes.