Abstract: Introduction Stroke prevention using oral anticoagulation (OAC) is the first management priority in atrial fibrillation (AF). Despite the importance of good therapy adherence, real-world adherence is still suboptimal. Patient education and adherence monitoring with new technologies are recommended. The main purpose of this sub-analysis of the AF-EduCare trial was to evaluate the effect of personalized follow-up strategies on adherence to OAC. Methods Regimen adherence was monitored by the electronic Medication Event Monitoring System cap at the start of the trial (M1) and after 12 months (M2), each for three months. Patients were part of one of three education groups (In-person, Online or App-based) or the standard care (SC) group. All are qualified for OAC therapy. Results A total of 768 patients were evaluated ( 11.8% SC vs. 86.8% any education group, mean age: 70.1 +/- 7.9 years). Patients were taking non-vitamin K OAC (once daily 53.8%; twice daily 35.9%) or vitamin K antagonists (9.4%), equally distributed over the different study arms (p = 0.457). Mean therapy adherence was high (M1:93.8 +/- 10.8%; M2:94.1 +/- 10.1%). During both monitoring periods, the education group scored significantly higher than SC (M1:94.2 +/- 10.0% vs. 91.3 +/- 15.0%; p = 0.027; M2:94.4 +/- 9.3% vs. 91.6 +/- 14.0%; p = 0.006). More patients in the In-person and Online groups were able to keep or improve their adherence to > 90% compared to the SC. Conclusion Overall adherence to OAC in all study groups, even in SC, was very high, without attrition over time. Nevertheless, targeted education led to a small but significantly improved adherence compared to SC.