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Object. Staphylococcus species are the most common organisms responsible for infection following implantable cerebrospinal fluid (CSF) diversionary procedures. The role of an antibiotic-impregnated shunt (AIS) system in the prevention of shunt infection has remained unclear because no human clinical trial has been reported on thus far. In this study, the authors assess an AIS system with respect to its prevention of shunt infection. Methods. Patients were prospectively randomized into groups to evaluate the efficacy of an AIS system against an identical control shunt system. The data accrued were subjected to a detailed statistical analysis. Logistic regression analysis was performed to determine the independent association between outcome and predictor variables. Shunt function analysis was also performed to compare the average time to infection between the two groups. One hundred ten patients were recruited; 60 received control shunt systems and 50 received AIS systems. Thirteen shunt infections were recorded (10 in the control group and three in the AIS group). Nine (69%) of 13 infections occurred within 2 months after shunt implantation (eight of 10 in the control group and one of three in the AIS group). Apart from one patient in whom no organism was identified, a total of 14 organisms (12 patients) were cultured from either the CSF (nine) or the shunt apparatus (three). Staphylococcus species accounted for the majority of shunt infections (83%): all 10 control shunts were found to have a positive culture of staphylococci, whereas none of the AISs had any staphylococci (p = 0.038). Conclusions. The AIS afforded antistaphylococcal protection, especially during the early postoperative period when most shunt infections are known to occur and throughout the follow-up period (median 9 months). The AIS system represents another important tool to enable the neurosurgeon to prevent shunt infections.