Erectile dysfunction (ED) is associated with clinical atherosclerosis and several atherosclerotic risk factors including smoking, hypertension, dyslipidemia, diabetes mellitus, obesity and sedentary lifestyle. Clinical atherosclerosis is also associated with these same risk factors and with biomarkers of inflammation, thrombosis, endothelial cell activation.We evaluated the crosssectional association between the degree of ED and levels of atherosclerotic biomarkers. A subcohort of 988 US male health professionals between the ages 46 and 81 years as part of an ongoing epidemiologic study had atherosclerotic biomarkers measured from blood collected in 1994-1995. These same men had in 2000, been retrospectively asked about erectile function in 1995 and in 2000. Biennial questionnaires since 1986 assessed medical conditions, medications, smoking, physical activity, body mass index, alcohol intake. The retrospective assessment of erectile function in 2000 for 1995 in these 988 men ranged from very good -28.2%, good -25.1%, fair -19.2%, poor -13.6%, to very poor -13.9%. Men with poor to very poor erectile function compared to men with good and very good erectile function had 2.9 the odds of having elevated Factor VII levels (P ¼ 0.03), 1.9 times the odds of having elevated vascular cell adhesion molecule (P ¼ 0.13) and 2.0 times the odds of having elevated intracellular adhesion molecule (P ¼ 0.06) and 2.1 times the odds of having elevated total cholesterol/high-density lipoprotein ratio (P ¼ 0.02) comparing the top to bottom quintiles for each atherosclerotic biomarker after multivariate adjustment. Lipoprotein(a), homocysteine, interleukin-6 and tumor necrosis factor receptor, C-reactive protein and fibrinogen were not associated with the degree of erectile function after adjustment. We conclude that selected biomarkers for endothelial function, thrombosis and dyslipidemia but not inflammation are associated with the degree of ED in this cross-sectional analysis. Future studies evaluating the prospective association of ED, endothelial function and cardiovascular disease appear warranted.