The impact of methicillin resistance on morbidity and mortality among patients with severe Staphylococcus aureus infection remains highly controversial. We retrospectively analyzed patients with mediastinitis due to methicillin-susceptible S. aureus (MSSA; 145 patients) or methicillin-resistant S. aureus (MRSA; 73 patients) who were treated with closed drainage using Redon catheters. Initial empirical antibiotic therapy was appropriate for every patient. Patients with MRSA mediastinitis were older, had higher disease severity scores at admission to the intensive care unit (ICU), and had longer periods of MRSA incubation. Multivariate analysis revealed that ICU mortality was associated with age of > or =65 years, incubation time of < or =15 days, bacteremia, higher Acute Physiology and Chronic Health Evaluation II score, and receipt of mechanical ventilation > or =2 days after surgical debridement, but not with methicillin resistance. After adjustment, durations of mechanical ventilation and Redon catheter drainage were similar for both groups (for patients infected with MRSA, only the time to mediastinal effluent sterilization remained longer). Methicillin resistance did not significantly affect ICU mortality among patients with poststernotomy mediastinitis who benefited from optimal treatments.