Direct oral anticoagulants such as dabigatran etexilate, rivaroxaban, apixaban, edoxaban, and betrixaban often interfere with clot-based or chromogenic coagulation assays and may lead to inaccurate results or render the test uninterpretable. Affected tests include many commonly ordered tests on hypercoagulable workup panels: lupus anticoagulant panels, activated protein C resistance, protein C and protein S activity, antithrombin activity, and specific factor activity levels. These tests should not be done in patients taking direct oral anticoagulants. If there is a compelling reason to perform these tests, great caution must be taken to avoid acting on a false result. For instance, specimens should be collected at the medication trough, and potential test interference should be considered prior to ordering. The potential for interference is dependent on test methodology, drug mechanism of action, and drug concentration. For patients suspected clinically to have antiphospholipid antibody syndrome, the lupus anticoagulant panel may be uninterpretable, but ELISA-based anticardiolipin and anti-beta2 GP1 antibody testing is unaffected. Genetic testing, such as polymerase chain reaction testing for factor V Leiden, is also unaffected.