Mediastinitis is a life-threatening complication among patients undergoing cardiac transplantation. There are conservative and aggressive surgical treatments. From October 1987 to October 2007, we reviewed the clinical records of 315 heart transplantations for those four cases with severe mediastinis needing surgical treatment for demographic data, clinical presentation, treatment, and outcome. Conservative therapy, such as sternal debridement without muscle flap closure and closed local irrigation with drainage, was performed in two cases. The other two patients needed aggressive surgical treatment with muscle flap or omental flap performed. Only one transplant recipient with severe mediastinis had undergone previous sternotomy before cardiac transplantation. The organisms were methicillin-resistant Staphylococcus aureus in three and Aspergillus fumigatus in one case. The one subject who received conservative therapy without a flap died. The other two with muscle flap and omental flap survived. Cardiac recipients survived if there was aggressive surgical treatment for severe mediastinitis. Meanwhile, we recommend prolonged aggressive antibiotic therapy and reduced immunotherapy.