Purpose: This study tested the hypothesis that a subset of secondary infrainguinal arterial reconstructions show prohibitive failure rates. Methods: Records of 79 consecutive patients, 44 men and 35 women, with a mean age of 60 years, who underwent secondary infrainguinal bypass from 1992 to 2000 at the University of Michigan Hospital, were reviewed. Data were analyzed with life-table analysis, logistic regression, and descriptive statistics. Results: Secondary infrainguinal reconstructions were performed in patients who had undergone earlier ipsilateral bypasses once (n = 35) or twice (n = 44). Among the prior procedures, 68% (n = 54) were done at an institution other than the authors'. Comorbidities included coronary artery disease (72%), tobacco use (77%), and diabetes mellitus (34%), but no patient had hemodialysis-dependent renal failure. Disabling claudication, with average ankle brachial index of 0.48, had been the indication for the primary operation in 77% of cases. Femoral-popliteal bypass was the primary procedure in 67%, with a prosthetic graft used in 62%. The mean patency duration of these earlier bypasses was 25 months. The indication for the final bypass was rest pain or tissue loss in 51% of patients, with an average ankle brachial index of 0.37. The most common procedure was a femoral-distal bypass with autologous vein (63%). Mean patency duration of the secondary bypasses was 30 months. Graft failure within 30 days of operation occurred in 22 patients (28%), and amputation was necessitated in 86% of these patients. The presence of rest pain or tissue loss, when accompanied with a history of early prior graft thrombosis in female patients, correlated with worse mean patency rates, recurrent graft failure (P ≤.05), and a 94% amputation rate. Men in a similar setting incurred a 57% amputation rate. No association of final patency existed with regard to age, number of prior bypasses, conduit types, tobacco use, or diabetes. Conclusion: Secondary infrainguinal bypasses are associated with an increased rate of graft failure and significant limb loss, particularly in those with a history of rest pain or tissue loss, female gender, and early prior graft failure. More appropriate initial operations in carefully selected patients and aggressive postoperative graft surveillance is speculated to improve these outcomes. (J Vasc Surg 2002;35:902-9.)