A previous prospective double-blind placebo-controlled study showed that cloxacillin prophylaxis significantly reduces the rate of infection after craniotomy. The purpose of the present follow-up study was to find out whether the data on routine cloxacillin prophylaxis would confirm the decreased infection rate after craniotomy. During this 1-year study, 8 infections occurred after 201 operations (4.0%) in 175 patients. No prophylaxis was given during 17 operations in 15 patients; 4 infections occurred in this group. The most frequently isolated microorganisms were Staphylococcus aureus, S. epidermidis, and Propionibacterium acnes, all of which were sensitive to cloxacillin. We conclude that cloxacillin is beneficial as prophylaxis in patients undergoing craniotomy.