Guideline-adherent care is associated with better patient outcomes, but whether this can be achieved by professional education is unclear. Here we conducted a cluster-randomized controlled trial across 70 centers in six countries to understand if a program for the education of healthcare professionals could improve patient-level adherence to clinical practice guidelines on atrial fibrillation (AF). Each center recruited patients with AF seen in routine practice (total N = 1,732), after which the centers were randomized, accounting for baseline guideline adherence to class I and III recommendations from the European Society of Cardiology on stroke prevention and rhythm control. Healthcare professionals in the intervention centers received a 16-week structured educational program with an average of 9 h of online engagement, whereas those at control centers received no additional education beyond standard practice. For the co-primary stroke prevention outcome, guideline adherence was 63.4% and 58.6% at baseline and 67.5% and 60.9% at 6-9-months follow-up for the intervention and control groups, respectively (adjusted risk ratio 1.10; 95% confidence interval (CI) 0.97 to 1.24; P = 0.13). For the co-primary rhythm control outcome, guideline adherence was 21.4% and 20.4% at baseline and 33.9% and 22.9% at follow-up for the intervention and control groups, respectively (adjusted risk ratio 1.51; 95% CI 1.04 to 2.18; P = 0.03). The secondary outcome of patient-reported integrated AF management showed a 5.1% improvement in the intervention group compared with the control group (95% CI 1.4% to 8.9%; P = 0.01). Thus, while the education of healthcare professionals improved substantial gaps in implementation for rhythm control, it had no significant effect on stroke prevention. ClinicalTrials.gov registration: NCT04396418 .