OBJECTIVES: The incidence and incremental additional cost of surgical site infections (SSIs) for common cardiothoracic surgical procedures are not well characterized. Our study was designed to estimate the cost of several higher volume inpatient cardiothoracic surgical procedures to better characterize the burden of SSIs to hospitals and the healthcare system. METHODS: The Premier Perspective™ Database (PPD) was used to estimate the incidence and costs for SSIs in several common cardiothoracic surgical procedures using ICD-9 codes discharged between Q2 2006 and Q1 2009 from the over 600 US hospitals included in the PPD. PPD is the largest hospital-based, service-level comparative database in the USA providing detailed resource utilization and cost data categorized under a patients’ principal and secondary diagnosis procedure codes. Our study focused on high volume cardiothoracic surgical procedures including sternum closure (3 codes), CABG (3 codes), and valve replacement (4 codes) to better estimate the incidence and costs of SSIs and the added costs to the healthcare system. RESULTS: The incidence of coded SSIs ranged between 1.9% to 6.3%, while the incremental additional costs for each SSI ranged between $30,395 and $67,722. The magnitude, therefore, of increased costs for each SSI was 2- to 6-fold higher compared with not having an SSI, depending on the cardiothoracic surgical procedure. CONCLUSIONS: The incidence of SSIs in several common cardiothoracic surgical procedures were relatively small (1.9%-6.3%), however, the increased costs ranged from 2- to 6-fold higher per SSI representing a substantial economic burden to hospitals in the US healthcare system. New healthcare interventions targeted towards reducing the incidence of SSIs for common cardiothoracic procedures along the patient-care continuum are likely to reduce costs in both the short and long-term for hospitals in the US healthcare system.