OBJECTIVES: Associated use of antithrombotics, antiplatelets and invasive strategies in patients with non ST-segment elevation acute coronary syndromes (NSTE-ACS) reduces cardiovascular events, however, with an increase in the risk of bleeding.  Clinical studies showed that fondaparinux is as effective as enoxaparin in treating patients with NSTE-ACS, but with reduced risk of bleeding events.  The objective was to determine the cost-effectiveness of fondaparinux versus enoxaparin in patients with NSTE-ACS in Brazil from the perspective of the Brazilian Ministry of Health (MoH). METHODS: An analytic decision tree model was conducted to estimate the resultant costs and consequences of the targeted therapies in patients with NSTE-ACS.  Model input data derived from the OASIS-5 study (N=20,078 NSTE-ACS patients randomized to fondaparinux or enoxaparin).  The analyzed outcome was a composite of cardiovascular events (i.e., death, acute myocardial infarction, stroke, and major bleedings).  Model time horizon was 9, 30, and 180 days post-NSTE-ACS.  Direct costs of NSTE-ACS events and treatments were computed (i.e., drugs, coronary angiography, myocardial revascularization, percutaneous intervention - PCI, hospitalizations, etc.).  Costs were expressed in 2010 Brazilian currency (1BRL=0.59USD).  Univariate and multivariate (Monte Carlo) analyses tested model robustness. RESULTS: At day 9, the average cost per patient treated was 2,575 for fondaparinux and 2,688 for enoxaparin.  Over 65% of total costs were attributed to the invasive treatment (PCI and revascularization). Drug costs (in-hospital therapies) accounted for 10% (fondaparinux) and 12% (enoxaparin) of total costs.  The estimated rates of cardiovascular events were 7.3% and 9.0% for fondaparinux and enoxaparin, respectively.  Results kept unchanged on days 30 and 180 post-NSTE-ACS.  Sensitivity analysis confirmed base-case results. CONCLUSIONS: Fondaparinux was dominant over enoxaparin (lower costs, better long-term benefits).  The budget impact after 5 years of anticoagulant substitution (at 20% constant adoption rate per year) could reach 90 million BRL in savings for the Brazilian MoH and healthcare system.