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Direct oral anticoagulants (DOAC) are used in several indications for the prevention and treatment of thrombotic events. As highlighted by data from clinical trials and case studies, all DOAC carry the risk of bleeding despite careful selection and patient management. Previous publications have demonstrated the limited knowledge of many physicians concerning the indications for, and correct management of, these anticoagulants. Health institutions should develop risk minimisation strategies and educational materials to prevent major adverse events related to DOAC administration. Major bleeding events are reported in clinical practice and specific antidotes are emerging from Phase III trials. Some antidotes are licensed but their high cost might limit routine use. We therefore illustrate approaches and tools that can help physicians prescribe DOAC appropriately. We focus on screening for modifiable bleeding risk factors and adapting doses according to the individual benefit-risk profile. We also provide recommendations on managing a missed dose, switching, bridging, and resumption.