OBJECTIVES: The National Institute for Health and Care Excellence in the United Kingdom (UK) recently issued guidance recommending the non-vitamin k antagonist oral anticoagulants (NOACs) rivaroxaban, dabigatran and apixaban for treatment and prevention of venous thromboembolism (VTE). An economic evaluation assessing apixaban versus rivaroxaban and dabigatran found apixaban was associated with greater quality-adjusted life-years (QALYs) gained at a lower cost. Edoxaban, another NOAC, is poised to enter the (ex-United States [US]) market for the same indication. This analysis therefore evaluated the cost-effectiveness of apixaban compared to low molecular weight heparin (LMWH) followed by edoxaban from the perspective of the UK National Health Service. METHODS:  A Markov model was developed to evaluate the lifetime clinical and economic impact of six-month treatment following a VTE event with apixaban versus LMWH/edoxaban. The model included the following health states: recurrent VTE, major bleed, clinically relevant non-major bleed, chronic thromboembolic pulmonary hypertension, and death. Transition rates among health states were based upon AMPLIFY and AMPLIFY-EXT clinical trial data, network meta-analyses, and UK life tables. Cost and utilities were based on published estimates. Price parity with apixaban was assumed in the absence of any pricing information for edoxaban. Outcomes were life-years gained, QALYs gained, costs estimated in 2012 British pounds, and the incremental cost-effectiveness ratio (ICER).  RESULTS: Six-month treatment with apixaban was predicted to increase life expectancy and QALYs as compared to LMWH/edoxaban over a lifetime horizon. When these treatments were priced at parity, apixaban was associated with cost-savings due to avoided bleeds and higher cost of LMWH. Dominance was maintained even when edoxaban was priced at an 18% discount to apixaban. One-way and probabilistic sensitivity analyses indicated that model conclusions were robust over a wide range of inputs.  CONCLUSIONS: Apixaban appears to be a dominant alternative to LMWH/edoxaban for the treatment and prevention of VTE.