Background: Surgical site infections (SSI) continue to be a significant problem in surgery. The American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) Best Practices Initiative compared process and structural characteristics among 117 private sector hospitals in an effort to define best practices aimed at preventing SSI. Study Design: Using standard NSQIP methodologies, we identified 20 low outlier and 13 high outlier hospitals for SSI using data from the ACS-NSQIP in 2006. Each hospital was administered a process of care survey, and site visits were conducted to five hospitals. Comparisons between the low and high outlier hospitals were made with regard to patient characteristics, operative variables, structural variables, and processes of care. Result: Hospitals that were high outliers for SSI had higher trainee-to-bed ratios (0.61 versus 0.25, p < 0.0001), and the operations took significantly longer (128.3 ± 104.3 minutes versus 102.7 ± 83.9 minutes, p < 0.001). Patients operated on at low outlier hospitals were less likely to present to the operating room anemic (4.9% versus 9.7%, p = 0.007) or to receive a transfusion (5.1% versus 8.0%, p = 0.03). In general, perioperative policies and practices were very similar between the low and high outlier hospitals, although low outlier hospitals were readily identified by site visitors. Overall, low outlier hospitals were smaller, efficient in the delivery of care, and experienced little operative staff turnover. Conclusions: Our findings suggest that evidence-based SSI prevention practices do not easily distinguish well from poorly performing hospitals. But structural and process of care characteristics of hospitals were found to have a significant association with good results.