We have successfully treated MRSA empyema after right pneumonectomy by the closed drainage and irrigation alone. The patient was a 70-year-old male who had received right pneumonectomy for p-III a squamous cell carcinoma originating in the right upper lobe bronchus. The operation wound was infected on the 6th postoperative day and became pleural fistula and finally MRSA empyema was developed on the 10th postoperative day. The chest drainage and irrigation of the infected pneumonectomy space with physiological saline containing antiseptic povidone iodine (Isodine) were performed 3 times a day for 14 days, however, the empyema was not cured completely. In addition, nausea and vomiting considered as the side effect of Isodine severely appeared. Therefore the antiseptic agent was exchanged to vancomycin hydrochloride from povidone iodine. Empyema space became sterile 4 days after the exchange and the drainage tube was removed 7 days after sterilization. Further empyema has not been developed for 8 months. We discussed the method and antiseptic agents in irrigation of empyema space.