OBJECTIVE: To investigate an outbreak of Staphylococcus aureus surgical-site infections. DESIGN: Case-control study. SETTING: Pediatric cardiothoracic surgery service of a tertiary-care university medical center. METHOD: Molecular typing was used to identify healthcare workers who carried the epidemic strain. RESULTS: Three children acquired surgical-site infections caused by a single strain of S. aureus. Fourteen (25%) of the staff members in the operating room and 17 (11%) on nursing units carried the epidemic strain (P =.01). A case-control study identified 4 healthcare workers who were associated statistically with the outbreak, 2 of whom (a cardiothoracic surgeon and a perfusionist) carried the epidemic strain in their nares. The surgeon also carried the epidemic strain on his hands. Each staff member who carried the epidemic strain was treated with mupirocin; those carrying the strain on their hands were required to wash their hands with chlorhexidine. The surgeon was not allowed to perform surgery until 2 of his hand cultures did not grow S. aureus. CONCLUSIONS: Only three children were infected with the epidemic strain, but it was disseminated widely among staff who cared for children who underwent cardiothoracic surgery. No additional cases were identified after staff members who carried the epidemic strain were decolonized. Both classic epidemiologic methods and molecular typing techniques were necessary to identify the source and extent of this outbreak.