OBJECTIVES: Low-molecular weight heparin (LMWH) followed by vitamin K antagonists (VKAs) are the current standard for the treatment of acute venous thromboembolism (VTE) and the prevention of recurrent VTE. Although the anticoagulation effect of VKA is considered strongly effective, the use is limited due to increased bleeding risks and a narrow therapeutic range. The direct oral anti-coagulant (DOAC) apixaban recently showed its non-inferiority in efficacy and superiority in preventing major bleeding compared to LMWH/VKAs in the AMPLIFY trial. The objective of this study was to calculate the cost-effectiveness of apixaban compared to LMWH/VKA in the treatment of acute VTE and prevention of recurrent VTE in the Netherlands. METHODS: A Markov model was designed in order to simulate a cohort of 1,000 VTE patients receiving either apixaban or LMWH/VKA. The transition probabilities were directly obtained from the AMPLIFY trial and the data for the costs and utilities were obtained from literature. The outcome of the analysis is the incremental cost-effectiveness ratio (ICER), calculated from the societal perspective. In the univariate and probabilistic sensitivity analyses (PSA) the robustness of the results was tested and various additional scenario analyses were conducted. RESULTS: In the base-case analysis, apixaban saved €236 and 0.044 quality-adjusted life years (QALYs) and 0.039 LYs were gained, compared to LMWH/VKA. In the univariate sensitivity analysis the model appeared to be robust. The results of 2,000 iterations in the PSA showed that the probability of apixaban being cost-effective at a willingness-to-pay threshold of €20,000/QALY was 100% and cost-saving 94%. The scenario of 18-month treatment duration was the only scenario not indicating cost-savings with an ICER of €425/QALY. CONCLUSIONS: Apixaban is an effective and cost-saving alternative to LMHW/VKA for the treatment of acute VTE and prevention of recurrent VTE in the Netherlands. The results appeared robust in sensitivity and scenario analyses.