Management of severe bleeding in patients taking oral anticoagulants is complicated. Acute care physicians must be knowledgeable about the individual oral anticoagulant agents, the general management of anticoagulant-associated bleeding, and the strategies for effective use of factor repletion and specific reversal agents. With any oral anticoagulant, minor or “nuisance” bleeding is most common and can be managed without repletion or reversal. Because the reversal agents are expensive and, like all therapies, have the potential for causing their own adverse events, acute care physicians must be sufficiently informed as to the risks and benefits before using these important new therapies. This program covers the role of the ANNEXA-4 Final Study results, published in February 2019 in the New England Journal of Medicine and management of severe bleeding.