OBJECTIVES: To evaluate the cost-effectiveness of the once daily oral anticoagulant rivaroxaban for prevention of stroke and systemic embolism in non-valvular atrial fibrillation (NVAF) patients from a UK payer perspective. METHODS: A Markov model was developed to evaluate cost-effectiveness over a lifetime time horizon. Costs and benefits were discounted at 3.5%. The patient population of interest were AF patients with one or more risk factors currently treated with warfarin. Clinical inputs were supplied from Safety-on-Treatment data from the Phase III ROCKET trial or informed by systematically reviewed literature. The Intention-to-Treat (ITT) dataset was also used in a sensitivity analysis. Warfarin efficacy data was adjusted to be reflective of the level of INR control found in Western Europe and baseline risk was adjusted to be reflective of the UK population.  Economic inputs were based on unit costs from the BNF, PSSRU and NHS Reference costs and resource use was from a dedicated observational study. Utility inputs were taken from a systematic review and included baseline utilities for AF, disutilities for clinical events and warfarin treatment. RESULTS: Base case analysis versus warfarin resulted in a total per patient incremental cost of £705 and an incremental QALY gain of 0.2459 with an estimated ICER of £2,869. The ITT analysis returned an ICER of £3,404, with an incremental cost of £775 and an incremental QALY of 0.2277. The sensitivity analyses found that the biggest drivers of the result were discontinuation rates, warfarin monitoring cost in primary care, warfarin disutility and frequency of warfarin monitoring.  The PSA indicates that the probability of rivaroxaban being cost-effective at a willingness-to-pay threshold of £20,000 is 97%. CONCLUSIONS: Rivaroxaban is a cost-effective alternative to warfarin in the prevention of stroke and systemic embolism in NVAF patients with one or more risk factors as evaluated from a UK payer perspective.