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Persistent (not intermittent) nasal carriage of Staphylococcus aureus is the determinant of CPD-related infections. Background We investigated the impact of staphylococcal carriage among patients on continuous peritoneal dialysis (CPD) in a university hospital. Methods Patients were screened for Staphylococcus aureus carriage and categorized as persistent, intermittent, or non– S. aureus nasal carriers. Patients were subsequently recultured every 12 weeks for S. aureus and coagulase negative staphylococcal (CoNS) carriage, and followed-up for CPD-related infections and antibiotic resistance. Results Fifty-two patients were included: 20 peristent, 10 intermittent, and 22 non– S. aureus carriers. Only persistent S. aureus carriage was significantly associated with an increased risk for all CPD-related infections [incidence rate ratio (IRR) 3.52 (95% CI: 2.56–4.85)], exit site infections [IRR 5.59 (95% CI: 3.50–8.92)], and peritonitis [IRR 2.19 (95% CI: 1.39–3.45)], as well as increased antibiotic use [IRR 3.43 (95% CI: 2.50–4.72)], including vancomycin [IRR 2.15 (95%: 2.13–2.16)]. No vancomycin-resistant S. aureus strains were detected. However, eight (2%) out of 407 CoNS strains isolated were vancomycin intermediately susceptible. In all five patients (four persistent and one intermittent carriers) concerned, this was significantly related to a higher antibiotic (including vancomycin) usage [IRR 2.65 (95% CI: 1.82–3.84)]. Conclusion Persistent—but not intermittent— S. aureus nasal carriage is the major determinant of CPD-related infections, and is associated with a significantly higher consumption of antibiotics, including vancomycin. The highly diverse population of CoNS appears to be the prime reservoir of staphylococcal vancomycin resistance. Accurate determination of the S. aureus nasal carriage state of CPD patients is essential to better target intervention strategies to prevent CPD-related infections.