Endothelial dysfunction plays an important role in the pathogenesis of cardiovascular diseases and diabetes mellitus. However, the causes underlying endothelial dysfunction are not fully understood. Therefore, the aim of the present study was to investigate associations of cardiovascular risk factors with soluble adhesion molecules (sE-Selectin, sICAM-1), soluble thrombomodulin (sTM) and von Willebrand factor (vWF) as markers of endothelial dysfunction. The study population consisted of a subcohort of 2,168 men and women aged 35 to 74 years randomly drawn from three cross-sectional population-based MONICA/KORA Augsburg surveys conducted between 1984 and 1995. In multivariable linear regression analysis, current smoking, high (versus moderate) alcohol consumption, ratio of total cholesterol/HDL-cholesterol (TC/HDL-C) and C-reactive protein (CRP) were significantly associated with elevated levels of sE-selectin and sICAM-1. Increased levels of sE-selectin were also found in subjects with actual hypertension, high body mass index and prevalent diabetes mellitus. In addition, low physical activity and no (versus moderate) alcohol consumption were significantly associated with elevated concentrations of sICAM-1. Levels of sTM were higher in subjects with actual hypertension, no or high amounts of alcohol intake and a high ratio of TC/HDL-C, but were lower in subjects with a history of myocardial infarction. VWF was significantly associated with CRP only. In conclusion, sE-selectin and sICAM-1 are more strongly associated with traditional cardiovascular risk factors than sTM and vWF.