Patients with peripheral arterial disease (PAD) are at increased risk for ESRD and cardiovascular events. The primary objective was to assess the association between ankle-brachial index (ABI) values and renal outcome. The secondary objective was to evaluate whether statins and angiotensin-converting enzyme inhibitors (ACEI) are associated with improved renal and cardiovascular outcome in patients with PAD. In a prospective observational cohort study of 1940 consecutive patients with PAD, ABI was measured and chronic statin and ACEI therapy was noted at baseline. Serial creatinine concentrations were obtained at baseline, 6 mo, and every year after enrollment. End points were ESRD, all-cause mortality, and cardiac events during a median follow-up period of 8 yr. Baseline estimated GFR <60 ml/min per 1.73 m(2) was assessed in 27% of patients. ESRD, all-cause mortality, and cardiac events occurred in 10, 46, and 31% of patients, respectively. In multivariate analysis, a lower baseline ABI was significantly associated with a higher progression rate of ESRD (hazard ratio [HR] per 0.10 decrease 1.34; 95% confidence interval [CI] 1.21 to 1.49). Chronic use of statins and ACEI were significantly associated with lower ESRD (HR 0.41 [95% CI 0.28 to 0.63] and 0.74 [95% CI 0.54 to 0.98], respectively), mortality (HR 0.66; [95% CI 0.55 to 0.82] and 0.84 [95% CI 78 to 0.95], respectively), and cardiac events (HR 0.71 [95% CI 0.56 to 0.91] and 0.81 [95% CI 0.68 to 0.96], respectively). In patients with PAD, low ABI values independently predict the onset of ESRD. Less progression toward ESRD and improved cardiovascular outcome was observed among patients who were on long-term statins and ACEI.