Purpose: Aorto-bifemoral bypass (AFB) is commonly performed in US hospitals. Durable long-term outcome is achieved after AFB performed to treat aortoiliac occlusive disease. However, short-term outcome for complex surgical procedures is not uniform across medical centers. The objective of the current study was to define the relationship of hospital volume to operative mortality after AFB. Methods: The study included 3073 patients with a primary procedure code for AFB and a diagnostic code for peripheral vascular occlusive disease who received treatment during 1997 at 483 hospitals in the Nationwide Inpatient Sample (NIS). The NIS represents a 20% stratified random sample representative of all US hospitals. Unadjusted and case mix-adjusted analyses were performed. Results: Overall AFB-related mortality was 3.3%. Hospitals that performed more than 25 AFB per year (33% of patients at 37 hospitals in the NIS) had a lower crude mortality rate (3.7% vs 2.2%) compared with hospitals that performed fewer AFB. In a multivariate analysis adjusting for case mix, AFB at a high-volume hospital was associated with 42% decreased risk for in-hospital mortality (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.34-0.97; P = .04) compared with low-volume hospitals. Two other important risk factors associated with increased mortality in the multivariate analysis included age more than 65 years (OR, 3.3; 95% CI, 2.0-5.4) and history of chronic pulmonary disease (OR, 1.9; 95% CI, 1.2-2.9). Conclusions: AFB operative mortality was significantly lower at high-volume hospitals in this nationally representative database. The effect of hospital volume of AFB procedures on outcome should be of importance to patients, providers, and health policy makers.