A 76-year-old woman received long-term immunosuppressive treatment for collagen vascular disease-associated interstitial pneumonia. The patient developed a cavitary mass lesion in the right lower lung field, and both nontuberculous mycobacteria and Aspergillus spp. were isolated after bronchial washing. The patient underwent a right lower lobectomy but developed Aspergillus empyema. Empyema due to Aspergillus spp. is a rare and life-threatening condition; however, the standard therapeutic strategies for treating Aspergillus empyema are not clear. We herein report a case of Aspergillus empyema that was successfully treated with a combination therapy which included open-window thoracostomy and the administration of antifungal agents (systemic micafungin and local amphotericin-B).