The efficacy of oxacillin as a prophylaxis for infection was analyzed in a 27-month randomized double-blind study of 400 patients who had undergone clean neurosurgical interventions lasting longer than 2 hours. Four neurosurgeons took part in the study and 356 patients were eligible for final analysis. Among the 171 patients treated with oxacillin, there was one case of infection (0.6%), compared to nine (4.9%) of the 185 patients given a placebo. The difference between the two groups was statistically significant (p = 0.0398). This study, together with others (randomized or not), clearly demonstrates the efficacy of antibiotic prophylaxis in prolonged clean neurosurgery.