Object: Despite many efforts at reduction, cerebrospinal fluid (CSF) shunt infections are a major cause of morbidity in shunt surgery, occurring in 5-15% of cases. To attempt to reduce the shunt infection rate at our institution, we added topical vancomycin (intrashunt and perishunt) to our existing shunt infection prevention protocol in 2012. Methods: We performed a retrospective cohort study comparing all shunted patients in January 2010 to December 2011 without vancomycin (control group, 263 procedures) to all patients who underwent shunt surgery between April 2012 and December 2015 with vancomycin (intervention group, 499 procedures). Results: The overall shunt infection rate significantly decreased from 6.8% (control group) to 3.0% (intervention group) (p = 0.023, absolute risk reduction 3.8%, relative risk reduction 56%). Multivariate logistic regression analysis confirmed that the addition of topical vancomycin showed that cases treated under a protocol of topical vancomycin were associated with a decreased shunt infection rate (odds ratio [OR] 0.49 95% CI 0.25-0.998; p=0.049). Age < 1 year was associated with an increased risk of infection (OR) 4.41, 95% CI 2,10-9,26; p=0.001). Time from surgery to infection was significantly prolonged in the intervention group (p=0.001). Conclusion: Adding intraoperative vancomycin to a shunt infection prevention protocol significantly reduces CSF shunt infection rate.