Background: Surgical site infection (SSI) is a major source of morbidity after infrainguinal lower extremity bypass (LEB). This study examines processes of care associated with in-hospital SSI after LEB and identifies factors that could potentially be modified to improve outcomes. Methods: The Society for Vascular Surgery (SVS) Vascular Quality Initiative (VQI) registry (2003 to 2012) was queried to identify in-hospital SSI after 7908 consecutive LEB procedures performed by 365 surgeons at 91 academic and community hospitals in 45 states. Variables associated with SSI were identified using multivariable logistic regression and hierarchical clustering. Expected and observed SSI rates were calculated for each hospital. Results: The overall in-hospital SSI rate after LEB was 4.8%. Univariate analysis showed that obesity, dialysis, tissue loss, preoperative ankle-brachial index <0.35, distal target, vein graft conduit, continuous incision for vein harvest, transfusion >2 units of packed red blood cells, procedure time >220 minutes, and estimated blood loss >100 mL were associated with higher SSI rates, whereas chlorhexidine (compared with iodine) skin preparation was protective. Multivariable analysis showed independent predictors of SSI included ankle-brachial index <0.35 (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.03-2.30, P < .04), transfusion >2 units (OR, 3.30; 95% CI, 2.17-5.02; P < .001), and procedure time >220 minutes (OR, 2.11; 95% CI, 1.05-4.23; P < .04). Chlorhexidine was protective against SSI (OR, 0.53; 95% CI, 0.35-0.79; P = .002). Stratified analyses based on the presence of tissue loss yielded similar results. Across VQI hospitals, observed SSI rates ranged from 0% to 30%, whereas expected SSI rates adjusted by the four independent predictors ranged from 0% to 7.2%. Conclusions: In-hospital SSI after LEB varies substantially across VQI hospitals. Three modifiable processes of care (transfusion rate, procedure time, and type of skin preparation) were identified and may be used by hospitals to reduce SSI rates. This study demonstrates the value of the SVS VQI detailed shared clinical registry to identify improvement opportunities directly pertinent to providers that are not available in typical administrative data sets.