Objectives: Median sternotomy (MS) wound infections are severe complications causing high morbidity and mortality after cardiac surgery. We aimed to develop a new Staphylococcus aureus mediastinitis and sternal osteomyelitis model in rats that can be used to evaluate the efficacy of new antimicrobial treatments. Methods and results: A complete MS wound was induced in anaesthetized rats. S. aureus was injected into the sternum. Kinetics of bacterial growth in the sternum (10 7 cfu/sternum) was assessed for histopathology and bacterial counts. A non-infected MS group served as a control. To evaluate antibiotic efficacy, 5 days of intraperitoneal vancomycin therapy (50 mg/kg, twice a day) was initiated 24 h following bacterial challenge. Macroscopic and histological examination confirmed that infection resulted in sternitis and mediastinitis. S. aureus bacterial counts in the sternum were inoculum-dependent, and it was proven that infecting rats with an inoculum of 10 7 cfu/sternum induced mediastinitis and sternal osteomyelitis. At this inoculum, bacterial counts in the infected sternum increased with time, reaching a maximum level of 2 + + + + + 1 3 10 7 cfu/g of sternum 8-12 days post-infection and then decreased with time to 2 3 10 4 cfu/g of sternum 20 days after infection. Histological changes paralleled bacterial counts. Vancomycin administration showed a protective effect against induction of sternal osteomyelitis; sternums from vancomycin-treated rats showed a significant decrease in S. aureus counts by 0.72 + + + + + 0.35 log cfu/g compared with untreated controls (P 5 0.0162). Conclusions: This new rat model of S. aureus sternal osteomyelitis and mediastinitis allows quantitative measurement of bacterial counts in the sternum. This model is reproducible and simple and thus suitable for the evaluation of new antimicrobials and new treatment modalities in MS infections