OBJECTIVES: Rivaroxaban (Xarelto®), an oral direct factor Xa inhibitor, represents a new OAC option for stroke prevention in patients with non-valvular atrial fibrillation (AF). The objective of this study was to assess the cost effectiveness of rivaroxaban in three European countries. METHODS: Markov models for Greece, Spain and Slovakia were developed to estimate the cost-effectiveness of rivaroxaban and vitamin K antagonist (VKA) treatment from the payer perspective of each country. In all three models, baseline event rates (adjusted to three month cycles) and relative treatment effects (HRs) were derived from the safety on treatment analysis of the ROCKET AF study and available literature. Utility values for events used to estimate the quality adjusted life years (QALY) were based on literature. Each model used costs and other economic inputs specific for that country. One-way and probabilistic sensitivity analyses (PSA) were performed. A subpopulation analysis was also conducted for Greece and Spain comparing rivaroxaban with VKA in patients with poor INR control (patients who spend less than 65% of time in therapeutic range). PSA were also performed to assess the robustness of the findings. RESULTS: Base-case analyses indicated that rivaroxaban was cost-effective with ICERs of €4,517, €17,432 and €11,274 per QALY compared with adjusted-dose warfarin for Greece, Slovakia and Spain, respectively. Rivaroxaban was found to be cost-effective in at willingness-to-pay thresholds for each country. The analyses conducted for patients with poor INR control found that rivaroxaban dominated VKA in this patient population in Greece, whereas an ICER of €2144 per QALY compared with VKAs were seen in Spain. PSA confirmed the robustness of the results. CONCLUSIONS: Rivaroxaban is a cost-effective alternative to VKAs for the prevention of stroke in patients with AF, particularly for those patients with poor INR control.