OBJECTIVES: To assess the cost-effectiveness of the novel fixed-dose anticogulant, rivaroxaban, in comparisson to the current dose-volatile standard of care, warfarin, for the prevention of stroke in high-risk atrial fibrillation patients. METHODS: A Markov model was constructed to model the costs and health outcomes of treatments, potential adverse events, and resulting health states over 35 years. Analyses were based on a hypothetical cohort of 65 year-old patients with chronic atrial fibrillation and high risk of stroke. The main outcome measure was cost per quality-adjusted-life-years (QALYs) gained over the lifetime and was assessed from the UK's National Health Service (NHS) perspective. Costs and utility data were drawn from previously published and publically available data, while event probabilities were adopted from both the literature and limited data from rivoroxaban’s phase III trial. RESULTS: Stroke prophylaxis with rivaroxaban offers lifetime health improvements over warfarin treatment, yet at substantial cost. From the NHS’ perspective, rivaroxaban’s baseline cost of £38,121 per QALY exceeds the typical willingness to pay threshold. Nonetheless, the results were sensitive to adjustments of several key variables, most notably the price of rivaroxaban, utility of warfarin, risk of bleeding-related events with warfarin, and discount rate for outcomes, justifying further consideration by NICE and the NHS. CONCLUSIONS: Novel anticoagulants such as rivaroxaban are one of many strategies being considered to replace standard warfarin therapy and mitigate its compounding weaknesses of frequent dose regulation and bleeding risk. Our results, though far from offering backbone for the substitution of rivaroxaban for warfarin treatment across the NHS, justify attention to this and other fixed-dose therapies as a potential alternative to warfarin-based stroke prevention strategies. In addition to more detailed subgroup analysis, further research ought to consider evaluating patient, caregiver, and indirect costs, long-term impacts on health-system demand, and comparing novel anticoagulation therapies against each other.