OBJECTIVES: Invasive fungal infections (IFI) remain a clinical concern in hematological cancer patients with prolonged neutropenia because they are major cause of morbidity and mortality.  As a result, the guidelines of the International Society of Infectious Diseases recommend adequate prophylaxis while the patient remains neutropenic.  In this study, a cost effectiveness analysis was conducted to measure the economic value of posaconazole as an alternative to fluconazole or itraconazole when used to prevent IFI in this patent population. METHODS: A decision analysis model was developed using clinical and economic data from randomized comparative trials, the economic literature and from expert opinion. The data were then used to estimate the incremental cost per life year saved with oral posaconazole prophylaxis relative to fluconazole or itraconazole from the Canadian provincial health care system perspective.  The base case results were then tested with an extensive sensitivity analysis which evaluated extremes in the incidence of IFI as well as variations in their cost of management. RESULTS: The base case findings revealed that prophylaxis with posaconazole provides at least comparable efficacy and an overall cost savings of approximately $4260 per patient.  Despite variations in the base case parameters, the sensitivity analysis suggested stability in the primary findings.  Posaconazole was associated with an overall cost savings (range = $1765 to $5118) and at least comparable benefit.  Optimal cost effectiveness was obtained when the drug was able to avoid more invasive Aspergillus infections. CONCLUSIONS: Prophylaxis with posaconazole in neutropenic hematological cancer patients is not only cost effective but also cost saving.  The economic benefits were due to the drug’s ability to reduce the incidence of high cost fungal infections, particularly Aspergillus species.