Background. The diagnosis of mediastinitis after open-heart surgery is infrequent but dreaded as it carries a high morbidity and mortality. The purpose of this study was to investigate the impact that topical antibacterials would have on the postoperative mediastinitis rate. Methods. Data were collected from 2455 consecutive patients who underwent sternotomy and cardiopulmonary bypass for both valvar and ischemic heart disease. Prior to 1999, patients (n = 1036) underwent surgery with standard perioperative intravenous antibiotics but no application of bacitracin. After 1999, patients (n = 1419) underwent surgery with intravenous antibiotics and application of bacitracin ointment to the sternotomy incision after closure. Results. Cases of mediastinitis occurred in 12 patients (1.2%) not treated with bacitracin, which required re-exploration, sternectomy, and soft tissue closure of the mediastinum. Alternatively, 3 patients (0.2%) in the group treated with bacitracin developed mediastinitis (P < .01). Therefore, the use of topical antibacterials was associated with a 6-fold reduction in the risk of mediastinitis after cardiac surgery. This significant difference in the infection rate was observed even though the percentage of patients with risk factors for mediastinitis was equal to greater than the group not treated with bacitracin. Non-bacitracin versus bacitracin: diabetics, 298 versus 484; emergency operations, 24 versus 50; bilateral internal thoracic grafts, 28 versus 29; and obesity (body mass index > 30), 294 versus 396. Conclusions. The use of topical antibacterials is associated with a decrease in the risk of mediastinitis after cardiac surgery.