OBJECTIVES:  To evaluate the cost-effectiveness of rivaroxaban compared to standard of care(SoC) with enoxaparin followed by dose-adjusted vitamin-K-antagonists for the treatment of Deep Vein Thrombosis(DVT) and Pulmonary Embolism(PE) in Greece. METHODS: An existing Markov model was locally adapted by a third-party payer perspective to reflect the management and complications of DVT and PE in the course of three-month cycles, up to death. The clinical inputs and utility values were extracted from published studies. Direct medical costs, obtained from local resources, were incorporated in the model and refer to year 2015. Both costs and outcomes were discounted at 3.5%. The incremental cost effectiveness ratio(ICER) per quality-adjusted-life year(QALY) gained was calculated. Probabilistic sensitivity analysis(PSA) was undertaken to deal with uncertainty. RESULTS:  The base case analysis showed that rivaroxaban in 3- and 6-month treatment duration for DVT and PE, respectively, as this is the common clinical practice in Greece, was associated with a 0.02 and 0.01 increment in QALYs compared to SoC, respectively. Rivaroxaban was associated with additional drug acquisition cost (€145 for DVT and €305 for PE), but reduced monitoring cost (-€47 for DVT and -€64 for PE) and events costs (-€152 for DVT and -€133 for PE). Therefore, rivaroxaban was a dominant (less costly, more effective) and cost-effective (ICER: €4,555) alternative over SoC for the management of DVT and PE, respectively. PSA revealed that the probability of rivaroxaban being cost-effective at a threshold of €34,000/QALY were 100% and 78% for DVT and PE, respectively. Rivaroxaban was found to be a cost-effective option compared to SoC when other treatment durations (6, 12 and 3, 12 months for patients with DVT and PE, respectively) were considered. CONCLUSIONS:  Rivaroxaban may represent a cost–effective option relative to SoC for the management of DVT and PE in Greece, regardless of the required treatment duration.