Direct oral anticoagulants (DOACs) have been established and already registered for clinical use on a wide basis in the United States and Europe. Different from the vitamin K antagonists (VKA), their mode of action is based on the direct inhibition of the single coagulation enzymes factor Xa or IIa. Other laboratory tests of hemostasis, such as the global tests prothrombin time (PT/INR) and activated partial thromboplastin time (APTT), or various functional coagulation assays involving generation of factor Xa or IIa for their endpoints, can be negatively influenced by the presence of the anticoagulant in the test sample. This interference has been well documented for rivaroxaban, apixaban, and dabigatran and is most prominent during the first hours after intake of the respective agent. Thus, the potential influence of DOACs has always to be considered when interpreting abnormal functional coagulation assays.