Objectives: to examine coagulation, fibrinolysis, and platelet activity in patients with peripheral vascular disease (PVD). Design: fifty consecutive PVD patients and 50 healthy volunteers. (Prospective comparative study). Materials and methods: P-selectin expression in non-fixed, whole blood was measured flow cytometrically on non-stimulated and ADP- and TRAP-6-stimulated samples. Plasma fibrinogen, von Willebrand factor (vWF), tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 were determined using standard techniques. Disease severity was stratified on the basis of the ankle-brachial pressure index (ABPI) and the angiographic data were assessed using the Bollinger score. Results: coagulation and fibrinolysis parameters as well as the P-selectin expression on both standard and non-stimulated platelets were significantly increased in patients vs controls (all P<0.01). The respective sensitivity and specificity were as follows: P-selectin expression (81%, 94%), vWF (72%, 86%), fibrinogen (64%, 98%), PAI-1 (44%, 90%, tPA (15%, 100%). P-selectin expression on TRAP-6-stimulated MP correlated with disease severity (r = 0.40, p < 0.01). Conclusions: these findings support the concept of ongoing thrombogenesis in the subclinical progression of PVD and demonstrate the high diagnostic sensitivity of flow cytometric analysis of platelet activation.