Endothelial dysfunction is thought to represent the initial stage in the development of atherosclerosis. Recently, noninvasive examination of endothelial function has become possible using flow-mediated endothelium-dependent dilation of the brachial artery (FMD) during reactive hyperemia. We examined whether FMD has prognostic value for the prediction of subsequent cardiovascular events. Patients were followed prospectively every month until the occurrence of the cardiovascular events. The study subjects comprised 221 consecutive patients (men 108, mean age 61.4+/-10.6, ischemic heart disease 152, cardiomyopathy 28, arrhythmia 12, valvular disease 5, congenital heart disease 3, and cardioneurosis 21). The mean FMD was 4.77+/-2.85% and this value was used to divide the patients into the 2 groups (Group 1: FMD > or =4.7%; Group 2: FMD <4.7%). There were 110 patients in Group 1 (men 36, mean age 60.5+/-10.9), and 111 patients in Group 2 (men 72, mean age 62.2+/-10.3). Patients were followed until the occurrence of at least 1 of the major clinical cardiovascular events. Seven cardiovascular events occurred in Group 1 (6.4%, 1.14 events per 100 patient-years), while 16 occurred in Group 2 (2.88 events per 100 patient-years). Kaplan-Meier analysis demonstrated a significantly higher probability of developing cardiovascular events in Group 2 than in Group 1. The present results demonstrated that the magnitude of FMD in the brachial artery was a good predictor of subsequent cardiovascular events.