Erectile dysfunction (ED) is especially common in men with major depressive disorder (MDD). This study examined the extent to which risk factors for cardiovascular disease (CVD) and vascular endothelial dysfunction were associated with ED severity in MDD patients. The sample included 46 middle-aged [M (s.d.)=53 (7) years], sedentary men diagnosed with MDD. ED severity was assessed by the Arizona Sexual Experiences Scale (ASEX), item 3. Depression severity was measured by the Beck Depression Inventory-II (BDI). The Framingham risk score was calculated as a composite measure of CVD risk factors. Vascular endothelial function was measured by flow-mediated dilation (FMD) of the brachial artery. Regression analysis showed that ASEX scores were predicted by the greater Framingham risk score (beta=0.41, P=0.008) and lower FMD (beta=-0.38, P=0.01), but not by BDI scores (beta=0.00, P=0.99). When FMD was included in the regression model, the relationship between Framingham risk and ASEX scores was partially attenuated (beta=0.27, P=0.08). ED was associated with greater CVD risk and impaired vascular endothelial function in depressed men. CVD risk factors may affect ED through impairment of vascular endothelial function.