Staphylococcus aureus has long been recognized as an important pathogen in human disease. Staphylococcal infections occur regularly in hospital patients and, despite antibiotic therapy, have severe consequences. An increasing number of such infections are caused by methicillin-resistant S. aureus (MRSA) strains, many of which have become multi-resistant to treatment. In an unblinded intervention trial, with historical controls, perioperative nasal carriage of S. aureus was eliminated using mupirocin nasal ointment. A significant reduction in surgical site infection was observed post-intervention in the treated group of patients. No resistant to mupirocin was observed. The results of this study warrant a prospective randomized, placebo-controlled study to confirm the efficacy of mupirocin.