OBJECTIVES: Venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE) is a common cardiovascular disorder. Acute VTE has been traditionally managed with short course parenteral anticoagulation followed by 3-6 months of a vitamin-K antagonist. Novel oral anticoagulants do not require routine coagulation monitoring and dose adjustment, thus potentially providing an alternative treatment option. The cost-effectiveness of dabigatran vs. rivaroxaban over a 6 months treatment course in the UK healthcare setting was evaluated in this research. METHODS: A life-time Markov model was developed, encompassing recurrent VTE events and VTE-related deaths, and the most common adverse events during anticoagulation therapy: major or clinically relevant bleeds (MCRB). The model was populated with data from pooled RE-COVER and RE-COVER II dabigatran trials and the 6 months treatment duration subgroup of the rivaroxaban EINSTEIN-DVT and EINSTEIN-PE trials. Long-term consequences of VTE were considered. Costs were analysed from the NHS and Public Social Services perspectives. Health outcomes were assessed in quality-adjusted life years (QALY). Utility values for modelled health states were EQ-5D data from RE-COVER studies, and published data. Probabilistic sensitivity analyses (PSA) were undertaken. RESULTS: In patients with index PE, 6 months treatment with dabigatran dominated treatment with rivaroxaban projecting less recurrent VTE and less MCRB at lower costs. Dabigatran was likely to remain cost-effective in 70% of cases at a threshold used in the UK of £30,000/QALY gained. Dabigatran continued to dominate treatment with rivaroxaban in patients with index DVT, projecting less non-fatal PE, less intra-cranial haemorrhages and less clinically relevant bleeds, but more recurrent DVT, with 68% likelihood of remaining cost-effective. In the pooled DVT/PE group, dabigatran dominated treatment with rivaroxaban and was 62% likely to remain cost-effective. CONCLUSIONS: Dabigatran is less costly and more effective than rivaroxaban when administered for 6 months after index PE, index DVT or both.