OBJECTIVES: Invasive fungal infections (IFI) from febrile neutropenia are associated with significant high mortality and expenditure. In two major clinical trials, voriconazole and caspofungin were recommended as alternatives to the mainstay of treatment. And two pharmaceutical therapies have been proposed in China but their cost-effectiveness is unknown. This study aims to compare the cost-effectiveness of IFI empiric treatment with caspofungin and voriconazole in patients undergoing febrile neutropenia in China.  METHODS: A decision analytic model was developed from the perspective of society.  Treatment transition probabilities in the antifungal therapy were obtained from two clinical trials. And the switched therapy after initial fungal therapy, duration as well as relevant tests and medication were derived from panel discussion of 16 Chinese clinical experts. Cost of medication, hospitalization, rescue and the relevant antifungal tests were considered and obtained from latest standard prices of medical services in China. Tree Age Pro 2011 software was used and the sensitivity analysis were performed to demonstrate the robustness of the model. RESULTS: The base case scenario demonstrated that caspofungin induced a higher probability of success (33.95% vs.25.63%), and a higher probability of survival (92.36% vs. 91.87%). The use of caspofungin also led to a lower expected mean cost per patient than voriconazole ($12,168 vs. $12,330). Comparing with voriconazole, caspofungin was preferred by $161, $12,266 and $246 per patient treated, successfully treated patient and patient survival, respectively. The result was moderately sensitive to the initial and switched therapy duration and acquisition cost of the antifungal agents. CONCLUSIONS: This is the first cost-effectiveness study of voriconazole vs. caspofungin for empirical therapy, and caspofungin seems to be a dominant strategy in the empirical antifungal therapy of febrile neutropenia. The study may be helpful to use evidence to inform the medical insurance formulary decision-making in Chinese health care setting.