OBJECTIVES: Posaconazole has shown superior clinical efficacy than Fluconazole / Itraconazole (FLU/ITRA) in the prevention of invasive fungal infections (IFIs) among patients with neutropenia resulting from chemotherapy for acute myelogenous leukemia (AML) or the myelodysplastic syndrome (MDS). Previous study has shown that Posaconazole is cost-effective versus FLU/ITRA in the 2007 U.S. health care setting.To reflect the changes in health care cost and the changes in drug prices, the study aims to provide an update on the cost-effectiveness of Posaconazole in the current U.S. health care setting. METHODS: A previously published (O'Sullivan et.al., VIH 2009) cost effectiveness model was used to assess the cost-effectiveness of posaconazole versus FLU /ITRA in the prevention of IFIs among patients with neutropenia resulting from chemotherapy for AML or MDS. Drug efficacy, mortality related to IFIs and death from other causes, were all estimated using data from a randomized clinical trial (Cornely et.al., NEJM 2007). IFI treatment costs were inflation-adjusted over last 6 years (2007-2012) and drug costs were based on 2012 IMS data. RESULTS: Trial data estimates the probability of an IFI over 100 days of follow-up while on Posaconazole to be lower than FLU /ITRA (0.05 vs. 0.11).The duration of treatment on Posaconazole is 25 days compared to 29 days with FLU or ITRA. Total costs of prophylaxis with FLU /ITRA and posaconazole is $5,293 and $5,859 respectively. The incremental cost-effectiveness ratios (ICER) for Posaconazole versus FLU/ITRA are estimated to be $8,805 per IFI avoided and $8,439 per life-year saved.  CONCLUSIONS: Posaconazole is cost-effective to FLU or ITRA in the prevention of IFIs among neutropenic patients with AML and MDS in the current U.S. health care setting.