Objective Many patients undergoing vascular surgical procedures are not on appropriate medical therapy. This study sought to examine the variation and impact of antiplatelet (AP) and statin therapy on early and late mortality in patients undergoing vascular surgery in our region. Methods We studied all patients (n = 14,489) undergoing elective carotid endarterectomy (n = 6978), carotid stenting (n = 524), and suprainguinal (n = 763) and infrainguinal bypass (n = 3053), as well as patients with known coronary risk factors undergoing open (n = 1044) and endovascular (n = 2127) abdominal aortic aneurysm repair from 2005 to 2012 in the Vascular Study Group of New England. Optimal medical management was defined as treatment with both AP and statin agents, preoperatively and at discharge. We analyzed temporal, procedural, and center variation of medication use. Multivariable analyses were used to determine the adjusted impact of AP and statin therapy on 30-day mortality and 5-year survival. Results Optimal medical management improved over the study interval (55% in 2005 to 68% in 2012; P trend < .01) with carotid interventions having the highest rates of optimal medications use (carotid artery stenting, 78%; carotid endarterectomy, 74%) and abdominal aortic aneurysm repair in patients with known cardiac risk factors having the lowest (open, 57%; endovascular aneurysm repair, 56%). Optimal medication use varied by center as well (range, 40%-86%). Preoperative AP and statin use was associated with reduced 30-day mortality (odds ratio, 0.76; 95% confidence interval [CI], 0.5-1.05; P = .09). AP and statin prescription at discharge was additive in survival benefit with improved 5-year survival (hazard ratio, 0.5; 95% CI, 0.4-0.7; P < .01) that was consistent across procedure types. Patients prescribed AP and statin at discharge had 5-year survival of 79% (95% CI, 77%-81%) compared with only 61% (95% CI, 52%-68%; P < .001) for patients on neither medication. Conclusions AP and statin therapy preoperatively and at discharge was associated with reduced 30-day mortality and an absolute 18% improved 5-year survival after vascular surgery. However, one-third of patients are suboptimally managed in real world practice. This demonstrates an opportunity for quality improvement that can substantially improve survival after vascular surgery.