Two specific endothelial cell products, von Willebrand factor and soluble E-selectin, were measured together with serum lipids, lipoprotein(a), systolic and diastolic blood pressure (SHP, DBP) in a follow up study of 162 patients attending a dedicated lipid clinic. Patients were further classified by the presence or absence of symptomatic vascular disease and smoking. After a mean of 49 months, 45 patients experienced a cardiovascular event (fatal or nonfatal myocardial infarction, stroke, or arterial surgery) and 11 developed non-cardiovascular diseases, including cancer. In univariate analysis, existing vascular disease (P < 0.01), increased levels of von Willebrand factor (P < 0.0001) and low density lipoprotein cholesterol (P < 0.02), greater age (P < 0.01), and lower levels of soluble E-selectin (P < 0.03) were all predictive of future vascular events. However, in multivariate analysis, only increased von Willebrand factor was predictive (P < 0.001). von Willebrand factor was also higher in patients who developed non-cardiovascular disease relative to those free of disease (P < 0.05). Our data support the hypothesis that increased levels of von Willebrand factor are an indicator of poor prognosis in patients with atherosclerosis or its risk factors.