OBJECTIVES: 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 healthcare system (SSN) perspective. METHODS: Two scenarios were compared within a three-year timeframe: the actual scenario, where patients are treated according to current clinical practice (46% with VKA, 38% with antiplatelets, 17% non-treated) and a scenario where Rivaroxaban is present with increasing market shares. The event risks (ischemic and haemorrhagic stroke, systemic embolism, myocardial infarction and bleedings) were retrieved from the ROCKET-AF trial or from a network meta-analysis. Resource consumption was computed using mean regional tariffs. Since Rivaroxaban price is not officially published, the daily cost used ranges from €2.10 (price of the first NOAC approved in this indication in Italy) and the lowest Rivaroxaban price available in Europe (€1.94).  The results of the analysis are displayed as a total costs difference between the two scenarios. RESULTS: A reduction in the total number of events and costs at SSN charge is shown since the first year from rivaroxaban introduction. The increase in pharmaceutical expenditure is offset by savings from a lower number of events to treat and absence of routine coagulation monitoring. CONCLUSIONS: The introduction of rivaroxaban in the national scenario is beneficial because it will provide a substantial reduction in the disease burden for patients and in costs for the SSN.