In the present study, we prospectively investigated the effects of once- or thrice-weekly prophylactic application of mupirocin to catheter exit sites on Staphylococcus aureus carriage, methicillin and mupirocin resistance, and catheter-related infections in continuous ambulatory peritoneal dialysis (CAPD) patients. We enrolled 36 CAPD patients (men/women: 21/ 15; mean age: 55.1 +/- 1.4 years) in the study. At the start of the study, patients had been on once-weekly mupirocin treatment for 3.1 +/- 2.0 years. They were then randomly assigned to use mupirocin either once weekly (group I; n = 18; men/women: 10/8; age: 55.3 +/- 1.8 years) or thrice weekly (group II; n = 18; men/women: 11/7; age: 55.0 +/- 2.3 years). During the study period, swabs were taken monthly from nares, axillae, the inguinal area, and the catheter exit site. We evaluated a total of 806 samples in the first 6 months of the study. The two study groups were similar in terms of age and sex. In group I, 5 isolations of S. aureus in 3 patients came from initial S. aureus carriers. During the first 6 months of the study, only 2 new S. aureus carriers were detected in group I, for a total of 7 isolations. Mupirocin resistance (MuR) was present in only 1 isolate and methicillin resistance (MeR) was not observed. In group II, no S. aureus carriers were present at the initial evaluation, and we encountered only 1 new S. aureus carrier during the first 6 months of the study. During the same period, MuR and MeR were absent in group II. During the 6 months, we observed 1 exit-site infection and 1 peritonitis episode attributable to coagulase-negative staphylococcus (CNS) in group I. In group II, we observed 1 exit-site infection attributable to CNS. During the first 6 months of the study, once- or thrice-weekly application of mupirocin to the catheter exit site has not led to any significant change in S. aureus carriage, MeR and MuR, or catheter-related infection in our CAPD patients.