Background The use of direct oral anticoagulants (DOAC) for stroke prevention in non-valvular atrial fibrillation (NVAF) has not been previously assessed in our setting. We aimed to describe sociodemographic, comorbidities, co-medication and risk of thromboembolic events and bleeding in patients with NVAF initiating oral anticoagulants (OAC) for stroke prevention, and to estimate adherence and persistence to OAC. Methods Population-based cohort study including all NVAF adult patients initiating OAC for stroke prevention in August 2013-December 2015. Persistence was measured in patients initiating OAC in August 2013-December 2014. Data source is SIDIAP, which captures electronic health records from Primary Health Care in the Catalan Health Institute, covering approximately 5.8 million people. Results 51,690 NVAF patients initiated OAC; 47,197 (91.3%) were naive to OAC and 32,404 initiated acenocoumarol (62.7%). Mean age was 72.8 years (SD 12.3) and 49.4% were women. Platelet-aggregation inhibitors were taken by 9,105 (17.6%) of the patients. For 22,075 patients, persistence was higher among the non-naive patients [n=258 (61.7%)] than among the naive [n=11,502 (53.1%)]. Adherence was estimated for patients initiating DOAC and was similar in naive and non-naive patients. Among the naive to DOAC treatment, those starting rivaroxaban showed a highest proportion [(n=360 (80.1%)] of good adherence at implementation (MPR>80%) while patients starting dabigatran were less adherent [n= 203 47.8%)]. Conclusions Acenocoumarol was the most frequently prescribed OAC as first therapy in NVAF patients. Non-naive to DOAC showed better persistence than naive. Rivaroxaban showed higher proportion of adherent patients during the implementation phase than apixaban and dabigatran the lowest.