OBJECTIVE This study assessed whether multisegmental disease that is severe enough to require an inflow procedure adversely affects infrainguinal bypass patency, limb salvage, or patient survival rates. METHODS The records of 495 patients who underwent 551 infrainguinal bypass grafting procedures were reviewed. Saphenous vein and prosthetic grafts were evaluated separately. Graft patency rates, patient limb salvage rates, and patient survival rates in those grafts that arose from a reconstructed inflow source were compared with those that arose from normal, nonreconstructed inflow sources. When grafts had either hemodynamic failure or occlusion, the cause of failure was identified. RESULTS Four-year primary patency rates in vein grafts that arose from a reconstructed inflow sources were lower than those in grafts that arose from nonreconstructed inflow sources (41% vs 54%; p = 0.006). Assisted primary patency rates and secondary patency rates, however, were similar (62% vs 74% and 64% vs 77%, respectively). The 4-year primary patency rate (45% vs 55%), assisted primary patency rate (60% vs 60%), and secondary patency rate (60% vs 61%) in prosthetic grafts did not vary based on inflow source. The most common cause of graft failure was inflow failure, except in the vein grafts that did not require an inflow procedure, in which the most common cause of failure was graft failure. Inflow failure occurred in 24% and 22% of the vein and prosthetic grafts with multisegmental disease, respectively, but in only 7% (p < 0.001) and 10% (p < 0.05), respectively, of those that arose from normal nonreconstructed inflow. The presence of an inflow procedure did not affect limb salvage rates or patient survival rates, regardless of graft material. CONCLUSIONS Long-term patency rates, patient limb salvage rates, and survival rates in patients with a reconstructed inflow source were similar to those of patients with a normal nonreconstructed inflow. A major cause of occlusion is inflow failure, and this occurs in a greater proportion of patients with multisegmental disease. These patients, in particular, may benefit from patient surveillance to screen for progression of their inflow disease and to allow for intervention before infrainguinal graft occlusion.