OBJECTIVES: Venous thromboembolism (VTE) encompasses pulmonary embolism (PE) and deep vein thrombosis (DVT). The standard of care is based on overlapped combined treatment including low molecular weight heparins (LMWH) plus vitamin K antagonists (VKA). An update of the clinical guidelines from ACCP recommends for patients with VTE and no cancer, as long-term anticoagulant therapy, the use of direct oral anticoagulants (DOAC) over VKA. Rivaroxaban, a DOAC, has proven similar efficacy to the combined treatment (LMWH plus VKA) and superior safety profile in randomized clinical trials (EINSTEIN program). The aim of this study was to estimate the cost-savings associated with rivaroxaban use in VTE treatment and recurrence prevention from the Spanish National Health System (NHS) perspective for the first three years from its funding. METHODS: A budget impact model was built based on the current clinical patterns used in patients with PE and DVT (LMWH monotherapy, VKA monotherapy and combined treatment) identified in an observational retrospective study conducted in Spain (EDITH study). An alternative scenario was defined assuming that rivaroxaban would replace LMWH monotherapy by 10%, 15% and 20% in the first, second and third year, respectively. The population included in the analysis was estimated from the annual VTE incidence in Spain. Only pharmacologic costs were considered. Unit costs were extracted from Spanish official sources. RESULTS: Introducing rivaroxaban for the treatment and recurrence prevention of VTE would result in €4,879,087, €7,319,477 and €9,765,773 savings in in the first, second and third year, respectively, for a total cost reduction of €21,964,338 over the three years. CONCLUSIONS: There is a prolonged use of LMWH according to the current clinical routine in Spain, resulting in an incremental cost for the public system. The progressive introduction of rivaroxaban would represent elevated savings in the treatment and prevention of DVT and PE for the Spanish NHS.