The objective of this study was to evaluate the effectiveness of mupirocin on Staphylococcus aureus with regard to peritoneal dialysis (PD)-catheter exit-site infections (ESI), tunnel infections (TI), and peritonitis episodes (PE). The study was performed on 42 continuous ambulatory peritoneal dialysis (CAPD) patients (group I) treated from April 1998 to July 1999. These patients were instructed to apply mupirocin daily at the catheter exit site as part of their exit-site care. The control was the same group's historical infection data. Results were also recorded for a second group of 16 patients (group II) with newly implanted PD catheters were also instructed to apply mupirocin at the exit site daily. During the control period (before daily mupirocin application), group I recorded 16 episodes of ESI (0.30 episodes per patient-year), 6 episodes of TI (0.11 episodes per patient-year), 15 episodes of PE (0.28 episodes per patient-year), and one case of catheter removal (0.019 episodes per patient-year) owing to S. aureus exit-site infection coexisting with peritonitis. The rate of S. aureus exit-site infection during this period was 0.11 episodes per patient-year; of S. aureus tunnel infection, 0.057 episodes per patient-year; and of S. aureus peritonitis, 0.076 episodes per patient-year. During the mupirocin period, infections and peritonitis owing to S. aureus dramatically decreased (p < 0.01 and p < 0.001 respectively). The rate of S. aureus exit-site infection was 0.02 episodes per patient-year, with no S. aureus tunnel infections, and no catheter removals owing to S. aureus peritonitis. Similarly, in group II, no episodes were recorded of any ESI, TI, or PE owing to S. aureus, although 4 episodes of ESI (0.37 episodes per patient-year, 2 with other gram-positive bacteria, and 2 with gram-negative bacteria) and 8 PEs (0.75 episodes per patient-year) were seen. We conclude that mupirocin application provides excellent prophylaxis for catheter-related infections owing to S. aureus, and that reduction of these infections may improve the long-term survival of patients on CAPD.