Staphylococcus aureus nasal carriage (SANC) is a risk factor for development of S. aureus dialysis-related infections. Reported here are results of a SANC surveillance and treatment program employed by our dialysis unit over a two-year period. Surveillance nasal cultures were performed at 3-month intervals in 129 peritoneal dialysis patients. Those with SANC applied mupirocin ointment intranasally 3 times daily for 5 consecutive days for 3 consecutive months. Treatment was repeated only when subsequent cultures showed SANC. Infection and catheter loss rates were compared to 63 historical controls, and between SANC and non SANC patients of the study group. Patients who were initially non carriers showed increasing probability for acquiring SANC throughout the study period. Following treatment, the probability for recurrence of SANC was 26%, 41%, 58%, and 62% at 1, 3, 6, and 12 months. The rates of S. aureus exit-site or tunnel infection (p = 0.36), peritonitis (p = 0.0002), and catheter loss (p = 0.01) were lower in the study group as compared to controls. Despite treatment, SANC patients demonstrated a twofold increase in exit-site/tunnel infection rate (p = 0.03) and a threefold increase in catheter loss rate (p = 0.1) as compared to non SANC patients. The high rate of SANC recurrence and the long interval between surveillance cultures may explain the failure of the current protocol to completely eliminate the risk for S. aureus infections. The results support a change in the treatment plan to that of continuing the monthly mupirocin regimen indefinitely once SANC has been identified.