Wound and graft infection can occur in more than 40% of patients undergoing vascular reconstructions for peripheral arterial disease (PAD). A recent increase in the frequency and severity of infections, as well as a change in the microorganisms recovered, led us to undertake a retrospective case-controlled study of wound/graft infections at this institution. The medical records of all patients undergoing vascular reconstruction for PAD during the previous 36 months were reviewed. Patient demographics, graft location and conduit, infection location, causative microorganisms, and factors potentially associated with development of infection were recorded. Infections were classified according to a modification of the CDC criteria into superficial incisional, deep incisional, or involving the graft (body only, anastomosis without disruption, or anastomosis with disruption). Univariate and multivariate regression analyses were used to identify factors associated with the development of infection. Four hundred ten (84 aortic, 41 extraanatomic, and 285 infrainguinal) revascularization procedures were performed in 217 men and 193 women with a mean age of 62 years (range 43-88). The infection rate for the entire group was 11.0% (45/410). Eighty percent (36/45) occurred after infrainguinal reconstructions and 64% (29/45) of the infections involved the groin incision. Direct involvement of the graft occurred in 67% (30/45), and 27% (12/45) presented with anastomotic disruption. Of the infrainguinal infections, in situ and prosthetic reconstructions were associated with a significantly higher rate of infection than reversed vein grafts tunneled anatomically (p <0.001, chi-square analysis). Patients with nonautogenous grafts (24 expanded polytetrafluoroethylene and 2 bovine) presented with more advanced infections involving the graft (20/26 procedures) and were more likely to present with anastomotic disruption (11/26). Staphylococcus aureus was isolated in the majority of infections (64%) and in all cases involving graft disruption. Multivariate regression analysis identified the following factors associated with development of infection: previous hospitalization (p = 0.03), a younger age (p = 0.047), and the presence of a groin incision (p = 0.04). Twenty-five percent of graft infections resulted in major amputation, and 11% of patients with graft infection died as a result. The incidence, morbidity, and mortality of infections in vascular reconstructions for PAD are increasing dramatically, particularly in infrainguinal reconstructions involving groin incisions. Perioperative antibiotic selection should be modified to include coverage for all Staphylococcal subspecies and hospitalization before surgical procedures should be avoided.