Endothelial vasodilator dysfunction is a characteristic feature of patients at risk for coronary atherosclerosis. Therefore, we prospectively investigated whether coronary endothelial dysfunction predicts disease progression and cardiovascular event rates. Coronary vasoreactivity was assessed in 147 patients using the endothelium-dependent dilator acetylcholine, sympathetic activation by cold pressor testing, dilator responses to increased blood flow, and dilation in response to nitroglycerin. Cardiovascular events (cardiovascular death, unstable angina, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary bypass grafting, ischemic stroke, or peripheral artery revascularization) served as outcome variables over a median follow-up period of 7.7 years. Patients suffering from cardiovascular events during follow-up (n=16) had significantly increased vasoconstrictor responses to acetylcholine infusion (P=0. 009) and cold pressor testing (P=0.002), as well as significantly blunted vasodilator responses to increased blood flow (P<0.001) and the intracoronary injection of nitroglycerin (P=0.001). Impaired endothelial and endothelium-independent coronary vasoreactivity were associated with a significantly higher incidence of cardiovascular events by Kaplan-Meier analysis. By multivariate analysis, all tests of coronary vasoreactivity were significant, independent predictors of a poor prognosis, even after adjustment for traditional cardiovascular risk factors or the presence of atherosclerosis itself. Coronary endothelial vasodilator dysfunction predicts long-term atherosclerotic disease progression and cardiovascular event rates. Thus, the assessment of coronary endothelial vasoreactivity can provide pivotal information as both a diagnostic and prognostic tool in patients at risk for coronary heart disease.