OBJECTIVE: Compare the total costs of antifungal therapy - lipid formulation of Amphotericin B (LAB), voriconazole (VCZ) and caspofungin (CAS) - as empirical treatment in Brazilian institutions/patients with high risk of infection by fluconazole-resistant Candida species. METHODS: A brazilian analytical model was constructed using the recommended protocols for resistant Candida infections in a 60-kg hypothetic patient and 21 days of treatment. The analysis perspective was from the third-part payers. Drug and device prices were retail prices (database: April/2005) including taxes. The daily impatients values used (without diagnostic testes and procedures) were obtained from hospitalar consultants (average of costs from medium-level hospitals in Sao Paulo). The studied scenarios were: 1) continuous use of intravenous therapy in full-time impatient condition; 2) switch from IV to oral with voriconazol in full-time impatient condition; and 3) switch from IV to oral with voriconazol and early discharge. RESULTS: The cumulative cost for LAB was R$81,080.37/US$32,432.15 and for CAS was R$ 50,697.38/US$20,278.95, without changes in all scenarios. Cumulative cost of VCZ has changed in each scenario and was R$38,382.34/US$15,352.94, R$26,991.93/US$10,796.77 and R$23,856.44/US$9,542.58 for the scenarios 1, 2 and 3, respectively. CONCLUSION: In high risk Candida-resistant scenario, VCZ has the lower cummulative cost than CAS and LAB (scenario 1). If the clinical situation allows the use of oral formulation, the advantage of VCZ increases significantly (scenario 2), mainly if the clinical status of patients permits discharge (scenario 3). Moreover, the oral and/or home treatment could reduce the risk of nosocomial infection, morbidity/mortality for immunocompromised patients and improve the QoL, but we couldn't measure these impacts because of lack of epidemiologic data in Brazil.