In Italy about 500,000 non-valvular atrial fibrillation (NVAF) patients have a major unmet medical need as they do not receive adequate anticoagulation therapy for stroke prophylaxis: many patients receive antiplatelet therapy, even when the guidelines recommend vitamin-K antagonists (VKA), or are not treated at all or have international normalized ratio inadequate control despite treatment with VKA. The purpose of this study was to perform a budget impact analysis of rivaroxaban – a novel oral anticoagulant (NOAC) – in NVAF patients with the highest unmet medical need from the Italian health care system (SSN) perspective.