OBJECTIVES: To evaluate the cost-effectiveness of caspofungin versus C-AmB for empirical antifungal therapy in patients with neutropenic fever from health care provider perspective in Thailand.     METHODS:  A decision-analytic model was used to project costs and outcomes of caspofungin versus C-AmB from treatment initiation until hospital discharge. Since there has not been a head-to-head comparative trial, an indirect treatment comparison was developed based on clinical trials that used the same 5-end point composite outcomes, including resolution of fever, resolution of baseline infection, absence of breakthrough infection, survival and no premature discontinuation. Patients were stratified by the presence or absence of baseline infection. Discontinuation because of nephrotoxicity or other adverse events were included in the model. Efficacy and safety data were based on Walsh 2004 (Scenario I) and Walsh 1999 (Scenario II). Life expectancy, quality of life, medical resource utilization and disease-related costs were obtained from the literatures and expert opinion. Drug prices were those published by Ministry of Public Health. All costs were expressed in THB 2013 values. RESULTS: Treatment with caspofungin increased life expectancy (LY) by 0.87 and 0.58 years, and resulted in additional 0.63 and 0.41 quality-adjusted life years (QALYS) when compared to C-AmB in Scenario I and II, respectively. In the base-case, use of caspofungin was cost saving in both scenarios. The results showed that caspofungin is cost-saving as long as the cost of treating nephrotoxicity is higher than 316,830 and 299,762 THB for the respective scenarios. The incremental cost-effectiveness ratio (ICER) increases if the cost of treating nephrotoxicity or the relative rate of nephrotoxicity decreases. Probabilistic sensitivity analysis supported the robustness of these findings.   CONCLUSIONS:  This is the first cost-effectiveness  of caspofungin as empirical treatment in Thailand. Caspofungin is more effective and less costly compared to C-AmB, and the use of caspofungin is anticipated to have both budgetary and health benefits.