Semi-invasive aspergillosis is a rare disease leading to severe complications even in fully immunocompetent patients. The therapeutic role of systemic and intrapleural antifungal agents remains not well known. We report herein the case of a 54-year-old woman who developed Aspergillus empyema invading the thoracic wall and subcutaneous tissues after completion pneumonectomy for aspergilloma. She initially was treated conservatively with systemic and intrapleural amphotericin B without any success and developed a severe anaphylactic reaction to intravenous liposomal amphotericin B (Ambisome). She then underwent an open-window thoracotomy with intrathoracic transposition of a latissimus dorsi muscle flap and was started on itraconazole therapy. The thoracostomy was closed after 6 months and the patient is doing well without any signs of recurrent infection after 3 years.