Objectives There has been a rapid increase in the number of endovascular procedures performed for peripheral artery disease, and especially aorto-iliac occlusive disease (AIOD). Results from single-center reports suggest a benefit for endovascular procedures; however, these benefits may not reflect general practice. We used a population-based analysis to determine predictors of clinical and economic outcomes following open and endovascular procedures for inpatients with AIOD. Methods All patients with AIOD who underwent open and endovascular procedures in the Healthcare Cost and Utilization Project Nationwide Inpatient Sample, 2004 to 2007, were identified. Independent patient- and provider-related characteristics were analyzed. Clinical outcomes included complications and mortality; economic outcomes included length of stay (LOS) and cost (2007 dollars). Outcomes were compared using χ2, ANOVA, and multivariate regression analysis. Results Four thousand, one hundred nineteen patients with AIOD were identified. Endovascular procedures increased by 18%. Patients who underwent endovascular procedures were more likely to be ≥65 years of age (46% vs 37%), female (54% vs 49%), and in the highest quartile of household income (20% vs 16%), all P < .05. Endovascular patients were more likely to be non-elective (41% vs 20%), in the highest comorbidity index group (8% vs 5%), and with iliac artery disease (67% vs 33%), all P ≤ .05. In bivariate analysis, endovascular procedures were associated with lower complication rates (16% vs 25%), shorter LOS (2.2 vs 5.8 days), and lower hospital costs ($13,661 vs $17,161), all P < .001. In multivariate analysis, endovascular procedures had significantly lower complication rates and cost, and shorter LOS. Conclusions Endovascular procedures have superior short-term clinical and economic outcomes compared with open procedures for the treatment of AIOD in the inpatient setting. Further studies are needed to examine long-term outcomes and access-related issues.