Emergency surgery, blood transfusion, and reoperation for bleeding have been associated with increased morbidity and mortality. Every effort is made to optimize patients preoperatively including cessation of oral anticoagulants in an attempt to normalize the coagulation profile. The recent explosive use of direct oral anticoagulants (DOACs) and antiplatelet medications has made the above more difficult. Cardiopulmonary bypass (CPB), with its associated fibrinolysis and platelet consumption, may exacerbate a pre-existing coagulopathy. In addition, the underlying surgical pathology, such as endocarditis accompanied by sepsis and disseminated intravascular coagulopathy (DIC) or aortic dissection requiring hypothermia and circulatory arrest, can aggravate an already challenged hematological profile. Ensuring a dry operative field upon entry by correcting the coagulopathy is offset by the concern of potentially hindering efforts to anticoagulate the patient in preparation for CPB, in addition to possibly creating a hypercoagulable state that could increase the risk of thromboembolic events. Management is challenging and decisions are typically made on a case-by-case basis. Surgery is delayed when possible and less invasive percutaneous options should be considered if feasible. If surgery is unavoidable, attention is paid to exercising meticulous techniques, avoiding excessive hypothermia, treating coexisting issues such as sepsis and correcting the coagulopathy with antidotes, reversal agents and blood products, with the understanding that a normal coagulation profile does not necessarily translate into hemostasis or the absence of thrombosis. Proper knowledge of the mechanism of action of the oral anticoagulants, available antidotes and their time to onset are essential in properly treating this difficult patient population.