The purpose of this study was to determine the relationship between erectile dysfunction (ED), coronary artery disease (CAD), and T(-786)C and intron 4 a/b endothelial nitric oxide synthase (eNOS) polymorphisms in 419 patients with suspected or known CAD referred for coronary angiography. The patients had a high prevalence of risk factors for both CAD and ED: hypercholesterolemia (64%), hypertension (74%), diabetes mellitus (25%), obesity (30%), and smoking (63%). Three hundred and twenty-one patients had significant coronary atherosclerosis (luminal diameter narrowing of 50% or more of at least 1 coronary artery), 41 had insignificant coronary stenoses, and 57 patients were found to have coronary arteries without the evidence of atherosclerosis. The prevalence of ED in these groups was 79%, 76%, and 67% (P = NS), respectively. As compared to patients without ED, those with ED exhibited significantly higher probability of having significant coronary atherosclerosis (69% vs 79%, P = 0.04), higher number of significant coronary stenoses (median, 1 vs 2, P = 0.004), and a higher prevalence of a triple-vessel disease (12% vs 25%, P = 0.004). We did not find any relationship between T(-786)C and intron 4 a/b polymorphisms and the manifestation of coronary atherosclerosis or the presence of ED. In conclusion, in patients with numerous cardiovascular risk factors referred for coronary angiography, there was a high prevalence of ED in patients with both the presence and the absence of coronary atherosclerosis. The coincidence of CAD and ED identified patients at increased risk of severe forms of CAD.