Abnormalities of the conduit, outflow tract, and graft hemodynamics are important elements in the mechanism of vein graft thrombosis, and their role must be defined when planning reoperation. In a consecutive series of 353 in situ saphenous vein bypass graftings performed for occlusive or aneurysmal disease, graft thrombosis occurred in 18 (5%) patients during the perioperative period and unexpectedly in 14 (4%) patients after discharge from the hospital. Assessment of graft hemodynamics (calculation of blood flow velocity) before thrombosis was helpful in predicting success after graft revision. Five grafts with known low flow (systolic flow velocity less than 40 cm/sec) that thrombosed in the perioperative period did not have patency restored by thrombectomy or graft replacement unless the outflow tract was also modified. If poor quality vein or technical error was the mechanism of thrombosis, translocation of the distal anastomosis to a proximal arterial segment (n = 4), and graft replacement with normal autologous vein (n = 5) or prosthetic graft (n = 1) were successful in relieving limb ischemia. After discharge from the hospital, unexpected graft thrombosis was successfully treated by a variety of secondary procedures (thrombolysis/thrombectomy, autologous or prosthetic replacement) if prior surveillance with duplex scanning demonstrated low flow as a result of graft stenosis (n = 7) or normal graft hemodynamics (n = 5). Prosthetic replacement of two failed bypass grafts with low flow caused by diseased outflow did not remain patent. Scrutiny of graft hemodynamics and limb arterial anatomy for alternative outflow sites can identify patients likely to benefit from reoperation after in situ bypass thrombosis.