OBJECTIVES: To evaluate the treatment cost of IFIs by comparing subjects who developed a proven or probable IFI to matched controls who did not. METHODS: Data were obtained by retrospective chart review in German hospitals using a non-randomized parallel group design in patients who have undergone remission induction chemotherapy for newly diagnosed or for first relapse of AML or MDS. IFI subjects had been diagnosed with proven or probable IFI according to EORTC criteria and received antifungal therapy. Match criteria were duration of febrile neutropenia, age and type of chemotherapy. Resource utilization data included length of stay, mechanical ventilation, parenteral nutrition, diagnostic procedures, antifungal agents and cost-intensive concomitant medication. Direct medical cost was calculated from the hospital provider perspective. RESULTS: A total of 108 patients were enrolled at 5 maximum care hospitals, 36 IFI patients and 72 controls. Mean age was 61.5 years (IFI group) and 61.2 years (control group), 50% and 63% were male, respectively. Primary diagnosis was AML in 97% of IFI patients and in 99% of control patients. The vast majority of IFI patients (74%) had invasive aspergillosis. IFI patients stayed on average 12 days longer in the hospital than control patients. In the IFI group all patients (100%) and in the control group 89% of patients received antifungal drugs. Mean direct cost per patient amounted to €51,517 in the IFI group and €30,454 in the control group. Incremental cost of €21,063 was dominated by cost for antifungal drugs (36%), hospital stay (32%) and blood products (23%). CONCLUSIONS: The economic burden of IFI in patients with AML or MDS is remarkable from the perspective of hospitals in Germany. Therefore, antifungal prophylaxis in patients with AML or MDS should be considered because of clinical and economic reasons.