<p>The impact of direct oral anticoagulants (DOACs) on platelet function is still unclear. We conducted an observational study aimed at assessing the effect of DOACs on platelet function in patients with atrial fibrillation (AF) treated with the direct thrombin inhibitor dabigatran (<i>n</i> = 22) and the Factor Xa (FXa) inhibitors rivaroxaban (<i>n</i> = 20), apixaban (<i>n</i> = 22) and edoxaban (<i>n</i> = 12), compared with patients treated with the vitamin K antagonist warfarin (<i>n</i> = 26) and with untreated patients without AF as controls (<i>n</i> = 23). We evaluated thrombin generation by calibrated automated thrombogram (CAT); light transmittance platelet aggregation (LTA) induced by adenosine diphosphate (ADP), thrombin, thrombin receptor-activating peptide (TRAP) and tissue factor (TF); serum thromboxane (TX) generation; the expressions of protease-activated receptor (PAR)-1 and P-selectin on the platelet surface. Thrombin generation was reduced in patients treated with FXa inhibitors as well as in patients treated with warfarin compared to controls. Patients treated with rivaroxaban and apixaban showed significantly reduced LTA compared to controls with all used agonists; while patients treated with dabigatran and edoxaban showed reduced thrombin- and TF-induced aggregation, respectively. TXB₂ production was reduced only in patients treated with FXa inhibitors. Patients treated with dabigatran and warfarin showed a higher proportion of activated platelets expressing P-selectin, and dabigatran-treated patients showed significantly higher expression of PAR-1 compared with controls. Our study shows that FXa inhibitors appear to have a more marked antiplatelet activity than dabigatran. These findings may be of relevance in differentiating specific effects and in selecting the most appropriate therapy for the individual patient.</p> Graphical abstract <p>Antiplatelet effects of oral anticoagulants.</p> <p></p>