OBJECTIVES: Non-ST elevation acute coronary syndrome (NSTE-ACS) imposes significant health and economic burden to Thai society. Anticoagulants are recommended as standard therapy by various clinical practice guidelines. With the advent of a new anticoagulant, therefore, this study aimed to determine the cost-effectiveness of fondaparinux versus enoxaparin in the treatment of NSTE-ACS in Thailand. METHODS: A two-part construct model composing of a one-year decision tree and a Markov model was developed to capture short and long-term costs and outcomes with the perspective of provider and society. Effectiveness data were derived from OASIS-5 trial while bleeding rates were derived from the Thai Acute Coronary Syndrome Registry (TACSR), the largest cohort study ever conducted in Thailand. Costs data were based on a Thai database and presented in the year of 2013. Both costs and outcomes were discounted with 3% annually. A series of sensitivity analyses were performed. RESULTS: The cost-effectiveness results showed that compared with enoxaparin, fondaparinux yielded cost saving (lower cost with greater effectiveness in both societal and provider perspectives). Total cost of major bleeding with revascularization had a great impact on amount of cost saved both in societal and provider perspectives. With a threshold of 160,000 THB (4,857.32 USD), fondaparinux showed above 95% being cost-effective compared with enoxaparin. CONCLUSIONS: Fondaparinux might be considered as another cost-effective alternative compared to enoxaparin in the era of limited healthcare resources in Thailand.