The importance of Staphylococcus aureus as etiological agent for catheter-related infections and peritonitis in peritoneal dialysis patients is well established. To evaluate groups at risk of developing Staphylococcus aureus infections, nasal and exit-site cultures were performed in 76 peritoneal dialysis patients monthly over a period of 3 yr. The risk of Staphylococcus aureus catheter infection was significantly higher in diabetic (group 1) and immunosuppressed (group 2) patients compared with nondiabetic and nonimmunosuppressed (group 3) patients. In diabetic patients, Staphylococcus aureus-positive nasal cultures were more frequent than positive cultures taken from the bland exit-site (73.3% versus 60.0%). On the other hand, both positive and negative exit-site cultures had a better prognostic value for Staphylococcus aureus catheter infection compared with nasal cultures. In immunosuppressed patients, both nasal and exit-site carriages were associated with a very high risk of Staphylococcus aureus catheter infection, but nasal swabs were far more often positive than swabs from the bland exit-site (72.7% versus 25.0%). However, the risk of infection was also high for non-nasal and non-exit-site carriers in this group. In nondiabetic and nonimmunosuppressed patients, the risk of Staphylococcus aureus catheter infection was increased only if two or more positive nasal cultures were detected. It is concluded that in diabetic patients, antibiotic prophylaxis should be performed in all Staphylococcus aureus exit-site carriers. All immunosuppressed patients should be treated prophylactically. In contrast, in nondiabetic and nonimmunosuppressed patients, prophylactic treatment should be considered only in nasal carriers with two or more positive cultures. The overall low peritonitis rate does not influence this prevention strategy.