OBJECTIVES: Over 500,000 cholecystectomies are performed in the U.S. annually. The incidence of surgical site infection (SSI) is higher after open compared to laparoscopic cholecystectomy, but other procedural risk factors for SSI have not been well established. We investigated operative risk factors for SSI following cholecystectomy in a large cohort of privately insured patients. METHODS: We performed a retrospective cohort study of persons aged 18–64 years with ICD-9-CM procedure or CPT-4 codes for cholecystectomy from 1/1/2004–12/31/2010 using commercial insurer claims data. Complex procedures and patients (e.g., cancer, end-stage renal disease) were excluded. SSIs occurring within 90 days after cholecystectomy were identified by ICD-9-CM diagnosis codes. Procedures in which SSI or septicemia was coded ≤30 days before  surgery were also excluded. Multivariable logistic regression was used to determine independent risk factors for SSI, controlling for age. RESULTS: A total of 113,138 cholecystectomy procedures were identified; 76% were performed in females and the median age was 43 years (range 18–64). A total of 833 (0.74%) SSIs occurred; the SSI incidence was higher for open procedures (90 [4.85%] open versus 743 [0.67%] laparoscopic; p<0.001). Independent risk factors for SSI included acute cholecystitis (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.32–1.77), choledocholithiasis (OR, 1.44; 95% CI, 1.10–1.88), open approach (OR, 5.51; 95% CI, 4.00–7.61) laparoscopic converted to open approach (OR, 5.48; 95% CI, 3.99–7.54), and concurrent bile duct repair (OR, 4.76; 95% CI, 1.93–11.70). Females had significantly decreased risk of SSI (OR, 0.75; 95% CI, 0.65–0.88). CONCLUSIONS: Acute cholecystitis, choledocholithiasis, and concurrent bile duct repair were associated with increased risk of SSI after cholecystectomy, controlling for open surgery, age, and gender. Our findings suggest that stratification of SSI rates by these operative factors is important when comparing rates between facilities.