We investigated prospectively the efficacy of sulbactam sodium/ampicillin sodium (SBT/ABPC), which is a combination drug of ampicillin and beta-lactamase inhibitor, as a preventive drug against postoperative infection in the field of neurological surgery. One hundred and six patients were given SBT/ABPC as follows: Before anesthetic induction at surgery, 1.5 g of SBT/ABPC was administrated by intravenous drip infusion, and further doses were continued at 12-hour intervals for 5 to 7 days. We assessed postoperative infection, type of surgery, duration of operation, and amount of hemorrhage. Search for related side effects and bacteriological examinations of the nasal cavity and throat before and after treatment were performed. The result was that postoperative infection was found in none of the patients. Adverse reactions due to SBT/ABPC such as apparent skin symptoms or gastrointestinal symptoms were not observed. Considering infections highly resistant to MRSA, SBT/ABPC would be effective to prevent postoperative infection in neurosurgical operations and could be used safely.