OBJECTIVES: In immunocompromised patients, presumed systemic fungal infections (PSFI) are treated empirically with an intravenous antifungal to reduce the occurrence of documented infections and associated mortality. In the Korean health care setting, conventional amphotericin B (CAB) is currently the single first line treatment choice. However, its toxicity often results in discontinuation or suboptimal dosing. Liposomal or lipid formulations of amphotericin B, with improved toxicity profile, remain restricted for second line use due to their high acquisition cost. The objective was to compare the cost-effectiveness of intravenous itraconazole (IVitra) with CAB as first line empirical treatment of presumed SFI in neutropenic cancer and bone marrow transplant (BMT) patients. METHODS: A medical decision tree was developed, including probabilities of toxicity, response, pathogen documentation and second line treatments. Clinical data were obtained from randomized trials comparing IVitra with CAB (n=392) and CAB with LAB (n=687). Resource use was obtained from a panel of clinical experts, unit costs from official sources (public payer perspective). Cost-effectiveness was expressed as cost per additional responder (defined as patient without fever or major toxicity). RESULTS: The total cost of PSFI per neutropenic cancer patient was lower for IVitra ($7234) than for CAB ($8023). The same cost ranking was obtained in BMT patients, however with higher hospitalization costs. The variables accounting for cost differences were first and second line antifungal drug costs and costs of concomitant drugs. In cost-effectiveness analysis, IVitra was dominant over CAB combining greater effectiveness (because of less toxicity) and lower costs. The result was robust to wide variations in expert reported medical practice. CONCLUSION: IVitra was shown to be a cost-effective and cost saving alternative to CAB for empirical treatment of presumed SFI in neutropenic cancer and BMT patients. These conclusions are in line with those obtained in different European countries, applying the same methodology.