Introduction: In this study, we aimed to analyze the effects of once- or thrice-weekly mupirocin application on peritonitis, exit-site infection (ESI), and antibiotic resistance with mupirocin. Patients and methods: By 2000 mupirocin began to be applied once a week to 33 patients who previously did not use mupirocin at the exit site. By the beginning of 2002, the patients were assigned to two groups. In group I patients continued to apply mupirocin once a week. In group II patients began to apply mupirocin to the exit site three times weekly and we began to obtain cultures from the nares, inguinal area, axillae, and the exit site. Results: A total of 28 episodes of ESI and 41 episodes of peritonitis were seen in 33 patients prior to mupirocin treatment, while a total of 14 episodes of ESI and 34 episodes of peritonitis were observed in all groups of patients who used mupirocin. In a subgroup analysis, 13 episodes of peritonitis and 7 episodes of ESI were determined in group I, while 6 episodes of peritonitis and 1 episode of ESI were determined in group II. Staphylococcus aureus reproduction rate and mupirocin resistance were 2.11 and 0.2%, respectively. Coagulase-negative staphylococcus reproduction rate was 70.56% (MuR: 59.87% and MeR: 33.7%) and 72.6% (MuR: 64.7% and MeR: 33.3%) in groups I and II, respectively. Conclusion: Mupirocin application at the exit sites reduces peritonitis and ESI to a considerable amount, and thrice-weekly application of mupirocin seems to be more efficient compared to once-weekly application.