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BACKGROUND: Antimicrobial guidance for common bile duct stones during the perioperative period is limited. We sought to examine the effect of broad-spectrum (BS) vs narrow-spectrum (NS) antibiotics on surgical site infections (SSIs) in patients with common bile duct stones undergoing same-admission cholecystectomy. STUDY DESIGN: We performed a post hoc analysis of a prospective, observational, multicenter study of patients undergoing same-admission cholecystectomy for choledocholithiasis and/or acute biliary pancreatitis between 2016 and 2019. We excluded patients with cholangitis, perforated cholecystitis, and nonbiliary infections on admission. Patients were divided based on receipt of BS or NS antibiotics. Our primary outcome was the incidence of SSIs, and secondary outcomes included hospital length of stay, acute kidney injury (AKI), and 30-day readmission for SSI. RESULTS: The cohort had 891 patients: 51.7% (n= 461) received BS antibiotics and 48.3% (n = 430) received NS antibiotics. Overall antibiotic duration was longer in the BS group than in the NS group (6 vs 4 d, p = 0.01); however, there was no difference in rates of SSI (0.9% vs 0.5%, p = 0.7) or 30-day readmission for SSI (1.1% vs 1.2%, p = 1.0). Hospital length of stay was significantly longer in the BS group (p < 0.001) as were rates of AKI (5% vs 1.4%, p = 0.001). On multivariable regression, BS antibiotic use was a risk factor for AKI (adjusted odds ratio 2.8, 95% CI 1.16 to 7.82, p = 0.02). CONCLUSION: The incidence of SSI and 30-day readmission for SSI was similar between antibiotic groups. However, BS antibiotic use was associated with a longer hospitalization and greater likelihood of AKI.