Abstract Background and Aims Searching for and treating nasal carriage of staphylococcus aureus in patients undergoing renal replacement therapy (RRT) has been debated. Indeed, previous meta-analyses showed that dialysis patients who were treated with intranasal mupirocin had lower rates of staphylococcus aureus infection but significantly more infections by other microorganisms. However, given the severity of staphylococcus aureus infections, it seems reasonable to detect and treat nasal carriers among patients on RRT. The aim of our study was to estimate the prevalence of staphylococcus aureus nasal carriage in patients on RRT, to evaluate the effectiveness of intranasal mupirocin in eradication of staphylococcus aureus and to detect the recolonization rate with the above microorganism after successful treatment. Method It was a single center prospective observational study. In 63 patients undergoing RRT (48 on hemodialysis and 15 on peritoneal dialysis) we performed cultures of the anterior nares to identify the carriage of staphylococcus aureus. Carriers then received intranasal mupirocin twice daily for seven days (in every nostril). Thirty days later, nasal cultures were repeated in those treated with mupirocin. In patients that were decolonized, new cultures were obtained three months after initial eradication of staphylococcus aureus had been detected. Results Nasal carriage of staphylococcus aureus was identified in 14 out of 63 patients (rate = 22%). Female sex was related with higher rate of nasal carriage (p = 0.014). All but one patient that received mupirocin were found decolonized after thirty days (cure rate = 92.8%). Recurrence of staphylococcus aureus nasal carriage was observed in 6 out of 13 patients that had successfully been treated (recurrence rate = 46%). Sex, age, renal replacement method, primary disease or previous immunosuppression treatment didn’t seem to significantly affect the possibility of recurrence. Conclusion Our study found a remarkable prevalence of staphylococcus aureus nasal carriage in patients on RRT. Intranasal mupirocin was highly effective in the eradication of the above microorganism, but nearly half of the successfully treated patients experienced a recurrence of nasal carriage. Further studies are needed to detect the effect of repeated mupirocin treatment to the nasal carriage status as well as to the rate of infection in the above population.