This study examines the long-term prognosis of patients with an abnormal exercise radionuclide angiogram in the absence of significant angiographic coronary artery disease (CAD). In general, patients without significant CAD have an excellent prognosis, but the long-term outcome for the subset of patients with an "ischemic" exercise test is not known. In this study, 161 patients with normal coronary arteries or insignificant CAD (< 50% left main and < 70% left anterior descending, left circumflex, or right), resting left ventricular (LV) ejection fraction > or = 0.50, and an abnormal exercise radionuclide angiogram (LV ejection fraction that decreased with exercise or peak exercise LV ejection fraction < 0.60) were followed for a median duration of 11.3 years. The mean delta LV ejection fraction was -0.07, 98 patients (61%) had a decrease in LV ejection fraction of > or = 5 units, and 40 patients (25%) had peak exercise LV ejection fraction < 0.50. During follow-up there were 19 deaths (only 1 of which was cardiac), 7 nonfatal myocardial infarctions, and 9 revascularization procedures. At 12 years, overall survival was 88%, better than the expected survival for the age- and sex-matched general population. Survival free of cardiac death or myocardial infarction was 94% and survival free of any cardiac event including revascularization was 88%. Thus, patients with an abnormal exercise radionuclide angiogram but without significant CAD have an excellent long-term prognosis.