- Background Direct oral anticoagulants (DOACs) are at least as effective as vitamin K antagonists (VKAs) for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). DOACs are associated with less intracranial hemorrhage and are easier to administer and therfore have become standard of care for stroke prevention in NVAF patients. Nevertheless, many eligible patients still receive no anticoagulation. The effect on overall mortality in routine practice of DOAC therapy compared to no anticoagulation in NVAF patients is unknown. Methods We identified all newly diagnosed, anticoagulant naive NVAF patients eligible for DOAC therapy from 2011 to 2016 in Clalit Health Services, the largest HMO in Israel. We created a matched cohort, using 1:1 propensity score matching of DOAC -treated versus non-anticoagulant treated NVAF patients. The primary outcome was overall mortality rate in the two cohorts. Secondary outcomes were rates of stroke , major cardiac and bleeding events. Results 28,195 newly diagnosed CHADS 2 ≥2 NVAF patients were identified. Of these 8 298 received a DOAC and 10 603 received no anticaogulation. The remainder received a VKA and were not included in this study. Patients recieving DOAC therapy were younger (77.4 vs 78.0 years), had a higher socioeconomic status (5.6 vs. 5.3), had a female predominance (53.7% vs 52.0%), had a higher BMI (29.6 vs 28.3) and had a greater prevalance of accompanying cardiovascular morbidities namely congestive heart failure (CHF) (29% vs 27%) and stroke (33% vs 30%) (P Conclusions In this cohort of newly diagnosed NVAF patients treated in routine clinical practice, DOAC therapy was associated with a lower risk for death compared to no oral anticoagulation. Our findings provide further evidence for the importance of DOAC therapy in NVAF patients. Disclosures No relevant conflicts of interest to declare.