Background: Mediastinitis resulting from surgical site infection may occur in 1% of patients undergoing median sternotomy. Methods: Case report and review of the pertinent English-language literature. Results: We report a case of mediastinitis caused by Acinetobacter baumannii, in a patient with multiple comorbidities who underwent cardiopulmonary bypass. Successful treatment consisted of surgical debridement, reconstruction, and ampicillin-sulbactam. Conclusions: Acinetobacter baumannii should be recognized as a potential causative agent of severe postoperative mediastinitis.