To evaluate the importance of nasal carriage of Staphylococcus aureus as a risk factor for the development of wound infection at the sternotomy site after cardiac surgery, a case-control study was done. The study population consisted of 1980 consecutive patients. Cases were all patients who developed a sternal wound infection from which S. aureus was cultured. Forty cases were identified, and 120 controls were selected. Preoperative nasal carriage of S. aureus, insulin-dependent diabetes mellitus, and younger age were identified as significant risk factors. The crude odds ratio of nasal carriage was 9.6 (95% confidence interval, 3.9-23.7). The median postoperative length of hospital stay for cases was 30 days longer than for controls. Mortality was also significantly higher for cases than for controls (10.0% and 0.8%, respectively).