Several studies found an increased risk of Staphylococcus aureus (SA) exit‐site and/or tunnel infections (ESI/TI) or peritonitis (P) in SA nasal carriers. The aim of our study was to determine efficacy of local preventive therapy with mupirocin in nasal carriers of SA. In this prospective study, from January 1997 to December 2003, 127 patients (pts) were included and observed for 4696 pt‐months. The ones with one or more positive smears were treated with mupirocin for five consecutive days, twice daily, every month. In acute or chronic ESI/TI with SA, the mupirocin was applied during daily exit‐site care. The pts with good or perfect exit‐sites were not treated. For statistic analysis, the proportion test and Pearson¢s correlation test were used. Among our pts the number of nasal carriers has decreased significantly ( P < 0.05) from 1997 (49.3%) to 2003 (18.0%). Simultaneously, the rates of SA peritonitis dropped from 0.032 episode/pt year in 1997 to 0.022 in 2003 ( P = 0.25). Significantly less ( P = 0.005) new SA ESI/TI were registered, from 0.113 episode/pt‐year in 1997 to 0.018 in 2001 and 0.022 in 2003. Two cases of mupirocin‐resistant SA were isolated, both in 2003, present in nasal as well as in ESI/TI swab. Diagnosis and treatment of SA nasal carriers among PD pts has proved to be important. The decrease in incidence of new ESI/TI was statistically significant, while peritonitis rates decreased less significantly. Mupirocin‐resistance in our study is low. When peritoneal catheter exit‐site is good or perfect, treatment with mupirocin is not necessary.