OBJECTIVES: To evaluate the cost-effectiveness of posaconazole versus fluconazole/ itraconazole in invasive fungal infection (IFI) prevention among patients with acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS) and at high risk of IFI due to chemotherapy-induced neutropenia in  Singapore. METHODS: A decision-analytic model previously developed for the US and other countries was adapted to Singapore, to estimate the cost-effectiveness of antifungal prophylaxis with posaconazole compared to fluconazole/ itraconazole among AML or MDS patients at high risk of IFI.  Patients were assumed to receive prophylaxis with posaconazole or fluconazole/ itraconazole.  Probabilities of IFI, IFI-related death, and other cause death within 100 days of follow-up were estimated from clinical trial data.  Trial results were extended to a lifetime horizon by modeling cancer-specific mortality, estimated from published sources, in one-month Markov cycles.  Prophylaxis and IFI treatment costs were estimated using data obtained from two hospitals in Singapore.  Model outputs include total costs (Singapore dollars (SGD); 1 SGD=0.82 USD), IFIs avoided, life-years saved, and incremental cost-effectiveness of posaconazole versus fluconazole/ itraconazole.  A probabilistic sensitivity analysis (PSA) was conducted, where probabilities of IFI, IFI-related death, and 100-day other cause mortality were assigned beta distributions from trial data. RESULTS: Total costs of prophylaxis with fluconazole/ itraconazole and posaconazole were SGD 4,475 and SGD 4,999, respectively.  Corresponding health outcomes were 0.11 and 0.05 IFIs and 2.44 and 2.51 life-years. Incremental cost-effectiveness ratios for posaconazole were SGD 8,150 per IFI avoided and SGD 7,526 per life-year saved.   Posaconazole was cost-effective compared to fluconazole/ itraconazole in 94% of PSA simulations at a threshold of SGD 80,000 (commonly cited threshold in Singapore). CONCLUSIONS: Use of posaconazole in place of fluconazole/ itraconazole for prevention of IFIs in a high-risk neutropenic population is cost-effective at a willingness-to-pay threshold of SGD 80,000 per life-year saved in Singapore.