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We have used a series of economic models to evaluate the differences in medical costs associated with the use of each of the four targeted-specific oral anticoagulants (TSOACs), dabigatran, rivaroxaban, apixaban, and edoxaban vs. warfarin for the treatment of nonvalvular atrial fibrillation (NVAF) and venous thromboembolism (VTE). All economic models were based on clinical event rates reported in published randomized phase III clinical trials, except one model used real-world data among patients with VTE. Incremental annual medical costs among NVAF and VTE patients with clinical events from a U.S. payer perspective were obtained from the literature and inflation adjusted to 2013 cost levels.