['Evidence suggesting a beneficial effect of cardioprotective medications in patients with lower extremity atherosclerosis derives largely from secondary prevention studies of heterogeneous populations. Patients with critical limb ischemia (CLI) have a large atherosclerotic burden with related high mortality. The effect of such therapies in this population is largely inferred and unproven.', 'The Project of Ex-Vivo vein graft Engineering via Transfection III (PREVENT III) cohort comprised 1404 patients with CLI who underwent lower extremity bypass grafting in a multicenter, randomized prospective trial testing the efficacy of edifoligide for the prevention of graft failure. Propensity scores were used to evaluate the influence of statins, beta-blockers, and antiplatelet agents on outcomes while adjusting for demographics, comorbidities, medications, and surgical variables that may influence drug use. Primary outcomes were major adverse cardiovascular events < or =30 days, vein graft patency, and 1-year survival assessed by Kaplan-Meier method. Potential determinants of 1-year survival were modeled using a multivariate Cox regression.', 'In this cohort, 636 patients (45%) were taking statins, 835 (59%) were taking beta-blockers, and 1121 (80%) were taking antiplatelet drugs. Perioperative major adverse cardiovascular events (7.8%) and early mortality (2.7%) were not measurably affected by the use of any drug class. Statin use was associated with a significant survival advantage at 1 year of 86% vs 81% (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.52-0.98; P = .03) by analysis of both unweighted and propensity score-weighted data. Use of beta-blockers and antiplatelet drugs had no appreciable impact on survival. None of the drug classes were associated with graft patency measures at 1 year. Significant predictors of 1-year mortality by Cox regression modeling were statin use (HR, 0.67; 95% CI, 0.51-0.90; P = .001), age >75 (HR, 2.1; 95% CI, 1.60-2.82; P = .001), coronary artery disease (HR, 1.5; 95% CI, 1.15-2.01; P = .001), chronic kidney disease stages 4 (HR, 2.0; 95% CI, 1.17-3.55; P = .001) and 5 (HR, 3.4; 95% CI, 2.39-4.73; P < .001), and tissue loss (HR, 1.9; 95% CI, 1.23-2.80; P = .003).'] Are statins independently associated with reduced mortality in patients undergoing infrainguinal bypass graft surgery for critical limb ischemia?