In order to describe the clinical features and outcome of Staphylococcus aureus meningitis, the charts of 44 cases seen at one teaching hospital during a 20-year period were retrospectively reviewed. Staphylococcus aureus was the fifth most common cause of bacterial meningitis (10.2% of cases). There were 28 (63%) cases of postoperative meningitis and 16 (37%) of spontaneous meningitis. Patients with postoperative meningitis were younger than patients with spontaneous meningitis (mean age, 40.3 vs. 59.3 years; P=0.04) and had a lower frequency of community-acquired infection (32.1% vs. 93.8%; P<0.01), severe underlying diseases (28% vs. 87%; P<0.01) and associated staphylococcal infection (35% vs. 75%; P=0.01). The clinical presentation was similar in both groups, but patients with postoperative meningitis had a lower frequency of altered mental status (39% vs. 75%; P=0.02), meningeal signs (28% vs. 62%; P=0.02), petechial rash (0% vs. 18%; P=0.04), bacteremia (7% vs. 75%; P<0.01), and septic shock (0% vs. 44%; P<0.01). Most patients were treated with cloxacillin or vancomycin, with or without rifampicin, for a mean period of 22.5 days (range, 1-100 days). Overall mortality was 27%, and the mortality rate was higher for cases of spontaneous than postoperative meningitis (50% vs. 14%; P=0.01). Mortality correlated significantly with advanced age, spontaneous meningitis, altered mental status, and the presence of severe underlying diseases, bacteremia, and septic shock.