The causes of autogenous saphenous vein (ASV) graft failure have been well described and are predominantly due to stenosis of the ASV graft during the first year after implantation. Distal atherosclerotic disease is a late cause of ASV graft failure. Furthermore, with failure of the ASV graft the clinical and hemodynamic status of the limb usually reverts to the preoperative state. To better define the causes and hemodynamic consequences of polytetrafluoroethylene (PTFE) graft failure, we reviewed the pathologic findings at surgery and compared these with arteriograms made prior to and after occlusion and sequential noninvasive hemodynamic studies in 36 patients with failed PTFE grafts (greater than 30 days after operation). Distal atherosclerotic disease was the most frequent cause of PTFE failure (23 of 36 limbs, or 64%), and it appeared as early as the first 6 months after implantation. Doppler pressures after PTFE failure deteriorated significantly (p less than 0.05) at the thigh, calf, and ankle levels. A blinded comparison of preoperative with postoperative arteriograms revealed significant progression of disease. Because of significant involvement of the popliteal artery in our series, treatment of intimal hyperplasia with patch angioplasty (seven cases, or 19%) was short lived and sequential extension was required. Distal atherosclerotic disease therefore appeared to be the most common cause of PTFE graft failure and occurred much earlier after implantation than with ASV graft failure. Deterioration of the hemodynamic state of the limb correlated with this high degree of distal atherosclerotic disease.