We investigated whether exercise radionuclide angiography provides prognostic information in addition to that identified by resting left ventricular function and coronary anatomy in patients with medically treated coronary artery disease. Clinical follow-up (median, 21.7 months) was obtained in 424 medically treated patients who underwent exercise radionuclide angiography and coronary angiography. The mean age of the study population was 58 years, and 67% were men. Cardiac death occurred in 16 patients, nonfatal myocardial infarction in 16, and nonfatal out-of-hospital cardiac arrest in 1. Univariate analysis showed that multiple variables were associated with future cardiac events, including number of diseased vessels, exercise and rest radionuclide ejection fraction, history of myocardial infarction, exercise and rest left ventricular end-systolic and end-diastolic volume indices, peak exercise workload, age, abnormal resting electrocardiogram, and peak exercise ST-segment depression. Only three variables were independently associated with cardiac events on follow-up: number of diseased vessels, radionuclide ejection fraction at rest, and age. In patients with three-vessel disease and a resting radionuclide ejection fraction of more than 40%, a subgroup with higher risk could not be identified on the basis of exercise radionuclide response.