Oral anticoagulant therapy (VKA) is nowadays the mainstay of treatment in primary and secondary stroke prevention in patients with atrial fibrillation. Given the limited risk-benefit ratio of vitamin K antagonists, pharmacological research has been directed towards the development of products that could overcome these limits, new oral anticoagulants were recently introduced: dabigatran, rivaroxaban, apixaban, and edoxaban.Scope of the present study was to examine patterns of use, effectiveness, safety and mean annual cost per patient of anticoagulant treatment for non-valvular AF in real clinical practice.A retrospective observational cohort study, by using administrative databases (drugs, hospitalizations, clinical visits, lab tests, population registry), was conducted in the Local Health Unit (LHU) of Treviso, Italy, from January 1, 2012 to December 31, 2016.5597 subjects were selected, 2171 of which satisfied all inclusion criteria. In particular 1355 patients were treated with VKA, 577 patients were treated with NOAC, and 239 patients were treated initially with VKA and subsequently switched to NOAC (switch group). NOAC treatment showed to be superior to VKA and this superiority was statistically significant on both end-points: patients in the NOAC group reported less cardiovascular events (9,9%) and less bleeding episodes (5,5%) versus VKA patients (14,6% and 11,4%; p<,0001 and p = 0,0049, respectively). The mean cost per patient per year was respectively € 1323,9 for patients treated with NOAC versus € 1003,3 for patients treated with VKA. Cost difference appears to be largely driven by drug cost (€ 767,9 for NOAC versus € 17,7 for VKA patients) and by specialist visits and laboratory tests (€ 318,4 for NOAC versus € 733,4 for VKA patients).In this retrospective real-world study treatment with NOAC showed to be associated with significant reductions of CV events and bleeding events compared to VKA use, albeit at a higher NHS' direct cost per patient/year, mainly due to higher drug therapy cost.