OBJECTIVES: Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common cardiovascular disorder. Acute VTE is typically managed with a short course parenteral anticoagulation followed by 3-6 months vitamin-K antagonist. Novel oral anticoagulants do not require routine anticoagulation monitoring and dose adjustments, thus potentially providing an alternative treatment option. The cost-effectiveness of dabigatran etexilate vs. edoxaban was evaluated over six months of treatment in the UK care setting. METHODS: A life-time Markov model was used, evaluating costs and quality-adjusted life years (QALY) of recurrent VTE (rVTE) and VTE-related deaths, and most common adverse events during anticoagulation treatment, major or clinically relevant bleeds (MCRB). The efficacy and safety of dabigatran were based on the pooled RE-COVER treatment studies, and indirectly compared with results of The Hokusai Study for edoxaban. Utility estimates for rVTE, bleedings and long-term consequences of VTE were sourced from RE-COVER studies, and from the literature. Costs were analysed from the perfective of the NHS and PSS. RESULTS: Following index VTE, six months treatment with dabigatran etexilate was less costly and improved patients’ quality of life when compared with six months edoxaban, assuming equal drug costs. Dabigatran projected more rVTEs overall, but less number of non-fatal PEs; dabigatran had less MCRB, hence the additional costs of rVTE were compensated by cost savings from avoidance of bleedings. Probabilistic sensitivity analyses showed 60% likelihood for dabigatran to be considered cost-effective at a willingness-to-pay of £30,000. Evaluating the model for treatment in a Western-European population, with efficacy and safety from corresponding sub-groups of RE-COVER studies, and The Hokusai Study, dabigatran etexilate was projected to be less expensive and to improve patients’ quality of life compared with edoxaban.    CONCLUSIONS: Dabigatran etexilate was projected less costly and safer than edoxaban when administered for six months following VTE.