Veins used for arterial bypass grafting undergo wall remodeling when exposed to altered flow, which may affect fibrinolytic mechanisms and subsequently the fate of the graft. Our aim was to study the extent of blood coagulation and fibrinolysis activation in 27 patients with patent grafts two years after femoro-distal bypass surgery. The two matched control groups included 10 and 19 conservatively treated patients having similar degree of arterial insufficiency (mean ankle/brachial blood pressure index) as the bypass group pre- and post-operatively, respectively. Plasma samples for coagulation and fibrinolysis activation were determined using ELISA and chromogenic assays. When compared with the control groups circulating tissue-type plasminogen activator antigen, and especially plasminogen activator inhibitor type-1, PAI-1 antigen and activity were significantly increased, the mean increase ranging between 54% and 140% in the bypass group. Thrombin-antithrombin III complex, fibrinogen, and C-reactive protein, did not differ, while triglycerides were elevated in the bypass group. Ten patients in the bypass group were insulin resistant, but this did not explain the differences in the fibrinolytic parameters between the bypassed and control patients. Patients with peripheral vein grafts had upregulation of PAI-1 in their circulation implying reduced fibrinolytic capacity. Increased PAI-1, a risk factor for venous thrombosis, might reflect developing intimal hyperplasia, and it remains to be studied whether upregulation of PAI-1 in venous grafts associates with graft failure.