Background: There are two important routes for the transmission of Staphylococcus aureus to the burn wound. In the endogenous route, patients naturally carrying S. aureus colonize their own wounds, whereas in the exogenous route burn wounds are cross-infected from other sources. in this study we evaluated the effect of blocking the endogenous route on S. aureus burn wound colonization by mupirocin application in the nose of patients at the time of admission. Methods: From September 2000 to January 2002 all patients with burns admitted to a single dedicated Burn Centre received nasal mupirocin upon admission. This period was compared to two control periods (CI: July 1999 to July 2000 and C2: January 2002 to, January 2003) for S. aureus burn wound colonization. The colonization risk was analysed, adjusting for confounding, with Cox proportional hazard regression. Results: A total of 98 patients did not have S. aureus burn wound colonization at the time of admission and were, thus, considered at risk for S. aureus acquisition during their stay. As compared to C1, the relative risk of acquiring S. aureus in their wound was 0.48 (95% CI: 0.24-0.97) in the mupirocin period and 0.55 (95% CI: 0.28-1.1) during the C2 period. S. aureus nasal/pharyngeal colonization was a significant independent risk factor for wound colonization (RR: 2.3; 95% CI: 1.2-4.2). Conclusion: Nasal mupirocin may contribute to risk reduction of S. aureus wound colonization in patients with burns. (C) 2007 Elsevier Ltd and ISBI. All rights reserved.