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Background: Packed RBC transfusion has been postulated to increase morbidity and mortality after cardiac/general surgical operations, but its effects after lower extremity bypass (LEB) have not been studied extensively., Study Design: Using the Vascular Study Group of New England's database (2003-2010), we examined 1,880 consecutive infrainguinal LEB performed for critical limb ischemia. Perioperative transfusion was categorized as 0 U, 1 to 2 U, and ≥3 U. Cohort frequency group matching was used to compare groups of patients receiving 1 to 2 U and 0 U with patients receiving ≥3 U using age, coronary artery disease, diabetes, urgency, and indication of revascularization. Primary end points were perioperative mortality, wound infection, and loss of primary graft patency at discharge, as well as 1-year mortality and loss of primary graft patency., Results: In the study cohort, 1,532 LEBs (81.5%) received 0 U, 248 LEBs (13.2%) received 1 to 2 U, and 100 LEBs (5.3%) received ≥3 U transfusion. In the study cohort and group frequency matched cohort, transfusion was associated with significantly higher perioperative wound infection (0 U:4.8% vs 1 to 2 U: 6.5% vs ≥3 U: 14.0%; p = 0.0004) and graft thrombosis at discharge (4.5% vs 7.7% vs 15.3%; p < 0.0001). At 1 year, there were no differences in infection or graft patency. In multivariate analysis, transfusion was independently associated with increased perioperative wound infection in the study cohort and group frequency matched cohort (1 to 2 U vs 0 U: adjusted odds ratio [OR] = 1.4; 95% CI, 0.8-2.5; p = 0.263; ≥3 U vs 0 U: OR = 3.5; 95% CI, 1.8-6.7; p = 0.0002; overall p = 0.002) and increased graft thrombosis at discharge (1 to 2 U vs 0 U: OR = 2.1; 95% CI, 1.2-3.6; p = 0.01; ≥3 U vs 0 U: OR = 4.8; 95% CI, 2.5-9.2; p < 0.0001, overall p < 0.0001)., Conclusions: Perioperative transfusion in patients undergoing LEB is associated with increased perioperative wound infection and graft thrombosis. From this observational study, it appears transfusion does not have major consequences during mid-term follow-up, but the presumed benefits of blood replacement should be weighed carefully because of the increased risk of perioperative complications with transfusion., (Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)