E ndothelial dysfunction is the initial step of atherosclerosis and plays an important role in the development of this condition.1,2 Measurement of flow-mediated vasodilation (FMD) of the brachial artery is a useful method for assessing endothelial function in humans.3-10 Appropriate interventions, including pharmacological therapy, supplementation therapy, and lifestyle modifications, are effective for improving endothelial function assessed by FMD in patients with cardiovascular diseases. [11][12][13][14][15][16] In addition, several lines of evidence have shown that FMD is an independent predictor of future cardiovascular events. [17][18][19][20][21][22] Nitroglycerine-induced vasodilation, an index of endothelium-independent vasodilation, assessed by sublingual administration of nitroglycerine has been used as a control test for FMD measurement to differentiate endothelium-dependent vasodilation from endothelium-independent vasodilation because both endogenous nitric oxide and administered nitroglycerine act on vascular smooth muscle cells. 4,[23][24][25][26] Recently, we demonstrated that nitroglycerine-induced vasodilation of the brachial artery decreased in relation to cumulative cardiovascular risk factors and was significantly correlated with cardiovascular risk factors as well as FMD in general population, including healthy subjects and patients with cardiovascular disease. 27 In addition, Schächinger et al 18 showed that impaired nitroglycerine-induced vasodilation of coronary Abstract-Measurement of nitroglycerine-induced vasodilation has been performed to differentiate endothelium-dependent vasodilation from endothelium-independent vasodilation as a control test for flow-mediated vasodilation (FMD). Recently, nitroglycerine-induced vasodilation per se has been reported to be a useful marker of the grade of atherosclerosis. The present study aimed to evaluate the prognostic value of FMD combined with nitroglycerine-induced vasodilation for future cardiovascular events. We measured FMD and nitroglycerine-induced vasodilation in 402 subjects, including patients with cardiovascular diseases. During a median follow-up period of 32.3 months, 38 first major cardiovascular events (death from cardiovascular causes, acute myocardial infarction, stroke, and coronary revascularization) occurred. Receiver-operator characteristic curve analysis revealed that FMD alone and nitroglycerine-induced vasodilation alone can predict cardiovascular events with areas under the curve of 0.671 (cutoff 3.3%) and 0.692 (cutoff 11.6%), respectively. FMD combined with nitroglycerine-induced vasodilation predicts cardiovascular events with an area under the curve of 0.701. After adjustment for age, sex, and cardiovascular risk factors, above cutoff FMD (≥3.3%) and below cutoff nitroglycerine-induced vasodilation (<11.6%; hazard ratio, 5.55; 95% confidence interval, 1.61-25.46; P=0.006) and below cutoff FMD (<3.3%) and below cutoff nitroglycerine-induced vasodilation (<11.6%; hazard ratio, 7.20; 95% confidence interval, 2.37-31.36...