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Patients undergoing allogeneic haematopoietic stem cell transplantation (allo HSCT) are at risk of developing invasive fungal infections ( IFIs). Even with introduction of oral triazole antifungal agents (fluconazole, itraconazole, posaconazole and voriconazole) IFI-associated morbidity and mortality rates and economic burden remain high. Despite their proven efficacy, it is currently unknown which is the most cost-effective antifungal prophylaxis ( AFP) agent. To determine the costs and outcomes associated with AFP, a decision-analytic model was used to simulate treatment in a hypothetical cohort of 1000 patients undergoing allo HSCT from the perspective of the Spanish National Health System. Generic itraconazole was the least costly AFP (€162) relative to fluconazole (€500), posaconazole oral suspension (€8628) or voriconazole (€6850). Compared with posaconazole, voriconazole was associated with the lowest number of breakthrough IFIs (36 vs 60); thus, the model predicted fewer deaths from breakthrough IFI for voriconazole (24) than posaconazole (33), and the lowest predicted costs associated with other licensed antifungal treatment and IFI treatment in a cohort of 1000. Voriconazole resulted in cost savings of €4707 per patient compared with posaconazole. Itraconazole demonstrated a high probability of being cost-effective. As primary AFP in allo HSCT patients 180 days posttransplant, voriconazole was more likely to be cost-effective than posaconazole regarding cost per additional IFI and additional death avoided. [ABSTRACT FROM AUTHOR]