Visceral obesity has been associated with an increased cardiovascular risk. However, the exact mechanisms are not completely clear. In this study we investigated the relationship between von Willebrand factor (vWF) and visceral adipose tissue (VAT) in a group of 181 overweight and obese premenopausal women visiting the weight management clinic of a university hospital. von Willebrand factor antigen (vWF:Ag), plasminogen activator inhibitor 1 (PAI-1) activity, VAT (computed tomography scan), insulin resistance (homeostasis model assessment of insulin resistance), and other anthropometric and metabolic parameters were measured. Subjects with VAT in the highest quintile had significantly higher levels of vWF:Ag (171+/-60 vs 129+/-40%; P=.001) and PAI-1 (24.7+/-8.5 vs 15.2+/-12.0 AU/mL; P<.001) compared with subjects in the lowest quintile. After correction for fat mass and homeostasis model assessment of insulin resistance the difference was still significant for vWF:Ag (P=.046), but not for PAI-1 (P>.05). Stepwise multiple regression analysis showed VAT and insulin resistance as independent determinants of vWF:Ag, whereas waist circumference, high-density lipoprotein cholesterol, and insulin resistance were independent determinants of PAI-1 activity. In a subgroup of 115 patients, we measured high-sensitivity C-reactive protein and found it to influence the relationship between VAT and vWF:Ag (r=0.16; P=.088), whereas the relationship with PAI-1 was still significant (r=0.21; P=.025). The results from this preliminary study suggest a plausible relation between visceral obesity and endothelial activation, possibly mediated by low-grade inflammation.