<p>Non-adherence and non-persistence of direct oral anticoagulants (DOAC) in patients with non-valvular atrial fibrillation remain major concerns. Most studies on non-persistence and non-adherence during the implementation phase (i.e., from the first to the last dose of DOAC) focus only on new DOAC users. We conducted a retrospective cohort study in France in 2018–2019 using the real-world THIN database to determine non-adherence during the implementation phase, non-persistence, and their associated factors among all DOAC users. Non-adherence was defined as the proportion of days covered &lt; 80% and non-persistence as a supply gap &gt; 30 days. Factors associated with non-adherence or non-persistence were identified using logistic regressions. We included a total of 5,059 DOAC users: 1,358 new users and 3,701 prevalent users. Non-adherence was 18.7% at 6 months and 24.2% at 1 year and non-persistence was 16.1% and 28.4%, respectively. Non-adherence was almost the same in new and prevalent DOAC users and non-persistence was slightly higher in new users. Factors associated with non-adherence and non-persistence were: age &lt; 65 years and having &lt; 5 comedications. Further studies will be needed to quantify the impact of non-adherence or non-persistence.</p>