Background: Plaque characteristics such as intraplaque hemorrhage (IPH) have been associated with secondary cardiovascular events (CVE) in patients undergoing carotid endarterectomy. In addition, carotid plaques containing macrophage infiltration or a large lipid core size were associated with less restenosis. It is currently unknown whether iliofemoral plaque histopathologic characteristics are predictive for secondary CVE in patients with peripheral arterial disease undergoing iliofemoral endarterectomy. The aim of this study was to examine the association between iliofemoral atherosclerotic plaque characteristics and secondary CVE in patients undergoing iliofemoral endarterectomy. Methods: There were 497 patients with iliofemoral atherosclerotic disease who underwent primary endarterectomy of the iliac or femoral artery from 2002 to 2013 included. All specimen were uptaken in the Athero Express biobank and 7 histologic plaque characteristics were analyzed: calcification, collagen, fat content, IPH, macrophages, smooth muscle cells, and vessel density. The composite CVE consisted of myocardial infarction, cerebrovascular accident, peripheral (re-)interventions, and cardiovascular death. Multivariate Cox regression models were used to examine the association between plaque and the composite end point during a follow-up period of 3 years. Results: Of the 497 patients, 225 (46.4%) experienced a composite CVE within 3 years after the initial surgery. Calcified plaques were univariably associated with composite CVE (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.00-1.73; P =.049). After correction for confounders, multivariable analyses showed no association between calcified plaques and composite CVE (HR, 1.13; 95% CI, 0.85-1.50; P =.413). IPH was not predictive of secondary CVE (HR, 1.02; 95% CI, 0.79-1.33; P =.867). Conclusions: In this cohort of patients with peripheral arterial disease undergoing iliofemoral endarterectomy, investigated atherosclerotic plaque characteristics were not independently associated with secondary CVE during follow-up.