OBJECTIVES: Vitamin K Antagonist (VKA) have traditionally been the main treatment for thromboembolic event prevention in atrial fibrillation (AF) and for the treatment of venous and pulmonary thromboembolic events (VTE) and the prevention of their relapses. A close patient monitoring with the determination of the INR (International Normalized Ratio) is needed during the AVK treatment, to avoid adverse thrombotic or hemorrhagic events. The improvement of the time spent in the therapeutic range (TTR), depending on INR results, has previously been studied in France with the use of a prescription assistance software (PAS). The use of this PAS improves the TTR from 58.46% to 71.79%. The objective of the analysis was to develop two cost effectiveness models taking into account the new management of the treatment of AF and VTE in France. The clinical and cost benefits of VKA (with/without the use of a PAS) has been evaluated versus new oral anticoagulants (NOAC): dabigatran, rivaroxaban and apixaban. METHODS: A Markov model was built for the treatment of AF and a decision tree for the treatment and prevention of VTE. In the VKA arms, both models integrate the possibility to adjust the percentage of time spent by patients within INR therapeutic range. In the VTE model, outcomes were expressed in cost per avoided event whereas in the AF model in cost per QALY. RESULTS: In both models, apixaban is the strategy producing the least thromboembolic and hemorrhagic events whereas AVK strategies are the cheapest treatments (2 to 2.5 times less than NOAC treatments). The use of the software for the treatment and prevention of VTE allows to save €3,192 per avoided event and for the AF treatment €7,557 per extra QALY gained and €6,688 per avoided event. CONCLUSIONS: Based on French guidelines for economic evaluation, apixaban and VKA + PAS are efficient strategies in AF.