OBJECTIVES: There are no studies carried out to date comparing the cost of systemic fungal infection treatment with voriconazole and caspofungin. The aim of the study was to estimate the in-hospital cost of voriconazole versus caspofungin, plus oral continuation therapy (OCT), for the treatment of invasive Candida and Aspergillosis infections in Spain. METHODS: A cost-minimization analysis model was performed from the hospital perspective in year 2004, as the same efficacy was assumed. Data on duration of treatment (intravenous + oral) and weight of patients were obtained from a local study: The Fungcost study. The incidence of drug-related adverse events was obtained from published clinical trials. Only direct cost for each episode were considered; medications (injectable and oral) at their hospital selling prices, the cost stemming from a drug-related adverse reactions treatment; and administration costs. Oral voriconazole was considered as the OCT for voriconazole arm, and oral fluconazol or itraconazol for caspofungin arm. Mean expected cost and incremental cost were calculated. Univariate and bivariate sensitivity analysis were carried out varying patient’s weight and intravenous treatment duration. RESULTS: The mean cost expected per episode (mean weight 68.6 Kg) was 6302.97€ (cost of intravenous treatment 5798.33€) for voriconazole, and 7487.29€ (6982.65€) for caspofungin in the treatment of invasive aspergillosis, with an incremental cost of 1184.32€. The treatment of candidiasis showed a mean costs of 6154.82€ (cost of intravenous treatment 5951.14€) and 7182.71€ (7169.49€), respectively, with an incremental cost of 1027.89€. Results were robust to any intravenous duration of treatment, and sensitive to an increase of patient’s weight above 103.3 Kg in aspergillosis and 101.1 Kg in candidiasis. CONCLUSIONS: Using costs and treatments patterns of fungal infections in Spain, voriconazole is more cost-effective than caspofungin in the treatment of invasive candidiasis and aspergillosis for patients below 101.1/103.3 kilograms, respectively.