Deep sternal wound infection (DSWI) is an uncommon but serious complication of median sternotomy in cardiac surgery, associated with significant mortality and morbidity. We performed a retrospective review of 30,102 consecutive cardiac surgical patients operated on at our institution from 1990 to 2003 and found an incidence of DSWI of 0.77%. The in-hospital mortality rate was 6.9% for DSWI patients versus 2.8% for patients without DSWI (P = 0.0002). Multivariable predictors for development of DSWI were old age, diabetes, previous stroke or TIA, and congestive heart failure. The use of bilateral internal thoracic artery (BITA) grafts increased the risk of DSWI in patients undergoing coronary artery bypass surgery, particularly in those with congestive heart failure alone or with diabetes. Skeletonization of BITA grafts resulted in a lower risk of DSWI, comparable to nondiabetic patients (1.3% versus 1.6%, P = 0.8). Patients with DSWI were treated with either sternal debridement and primary closure or sternectomy with myocutaneous flap reconstruction, resulting in a 6-month freedom from adverse event rate of 76% in both groups.