OBJECTIVES: In allogeneic transplant (allo-SCT) recipients with graft-versus-host disease (GVHD) the risk of contracting an invasive fungal infection (IFI) is high and antifungal prophylaxis to prevent IFIs is routinely given. Fluconazole, has been standard antifungal prophylaxis in GVHD-patients in Sweden. Recently many Swedish centers have switched from fluconazole, which lacks efficacy against Aspergillus, to posaconazole, for the prevention of IFIs in GVHD-patients receiving moderate to high doses of glucocorticoids. Although, the superior efficacy of posaconazole vs. fluconazole in preventing IFIs have been demonstrated in this clinical setting, the cost-effectiveness of posaconazole vs. fluconazole for GVHD-patients in Sweden has not been established. The aim of this analysis is to estimate the cost-effectiveness of posacoanzole vs. fluconazole prophylaxis in allo-SCT recipients with severe GVHD receiving immunosuppressive therapy in Sweden. METHODS: A decision-analytic model was used to determine life-time outcomes of patients with GVHD at high risk of contracting IFIs. The model outcomes were quality adjusted life years (QALYs), costs associated with IFI-prophylaxis and treatment of IFIs and the incremental cost-utility ratio. The efficacy data were gathered from a clinical trial comparing posaconazole with fluconazole prophylaxis in patients with GVHD. The resource use for treatment of IFIs was gathered by expert opinion. Utility, mortality and unit costs were gathered from the literature. To assess the uncertainty of the modeled outcomes a probabilistic sensitivity analysis (PSA) was developed. RESULTS: The incremental cost-utility ratio of posaconazole vs. fluconazole for the prevention of IFI in GVHD-patients in Sweden was 541,628 SEK/QALY. The PSA showed a 56.4% probability for a cost per QALY less than 600,000 SEK. CONCLUSIONS: Given a willingness-to-pay threshold of 600,000 SEK/QALY, posaconazole is likely to be cost-effective for preventing IFIs in GVHD-patients compared to fluconazole.