OBJECTIVES: The rising incidence of invasive fungal infections (IFI), especially invasive aspergillosis, compromises therapeutic outcomes in haematologic cancer patients and in transplant recipients.The aim of our analysis was to determine the cost-effectiveness of prophylaxis with posaconazole in comparison with standard azole therapy (fluconazole or itraconazole) for risk haematology patients in Czech Republic. METHODS: The decision-tree economic model was developed for patients with acute myelogenous leukemia (AML). The rates of IFI, IFI-related mortality, overall mortality and treatment duration were obtained from randomised controlled trials.The cost of drugs and IFI hospitalisation was obtained from panel of experts. The model estimates total costs, numbers of IFIs, and life-years gained (LYG) per patient in each prophylaxis group. Cost and health effects were discounted at 3%. RESULTS: In comparison with fluconazole/itraconazole prophylaxis, posaconazole prophylaxis was associated with significant reduction in the rates of IFI in AML patients, lower IFI-related deaths and increased life years. Accumulated cost to the Czech health care system per patient receiving the posaconazole regimen was €2770 compared to €2090 for the fluconazole/itraconazole regimen. This results in an incremental cost of €680 per patient. Incremental life-years saved were 0.016 per patient. The corresponding incremental cost effectiveness ratio (ICER) is €42,122 per LYG. Probabilistic sensitivity analysis tested numerous assumptions about the model cost and efficacy parameters and found that the results were robust to most changes CONCLUSIONS: In addition to the proven efficacy, posaconazole appeared to be cost-effective relative to fluconazole/itraconazole in the prophylaxis of IFIs among patients with AML in the settings of Czech Republic health care.