Aspergillus pleural empyema is a rare but often fatal infection complicating thoracic surgery. Three men and one woman aged 23-47 years were diagnosed with Aspergillus pleural empyema after lung resection. Underlying diseases were lung cancer (n = 2), Hodgkin's disease (n = 1) and thoracic trauma (n = 1). The treatment protocol consisted of systemic anti-fungal treatment with caspofungin and voriconazole, intrapleural application of amphotericin B and surgical debridement with secondary closure of the leaking bronchial stump. Two patients with chronic Aspergillus pleural empyema had been pretreated with itraconazole and/or amphotericin B. Two patients were treated with a thoracostoma. Two patients had undergone pneumonectomy for previously diagnosed pulmonary aspergillosis. Caspofungin was given for 13-60 days, Voriconazole for up to 100 days. Surgical debridement was performed in all cases and in two cases the created thoracostoma was closed during a second surgical procedure. Aspergillus PCR using blood samples, bronchoalveolar lavage or aspiration fluid was used for monitoring. All four patients had complete clinical and microbiological remission. Our case series shows promising results and underscores the importance of a combined therapeutic approach for Aspergillus pleural empyema consisting of anti-fungal treatment and surgery. Voriconazole and caspofungin seem to be a suitable combination for this infection.