Monitoring unfractionated heparin (UFH) to ensure effective anticoagulation may be performed using anti-factor Xa activity (anti-Xa) instead of the activated partial thromboplastin time. However, in patients who have been treated with oral factor Xa (FXa) inhibitors (apixaban, rivaroxaban, and edoxaban) while switching to UFH therapy, there is a risk that these oral anti-FXa drugs could interfere with UFH calibrated anti-Xa monitoring. This may lead to inappropriate anticoagulation management. This report of the ISTH Subcommittee on Control of Anticoagulation summarizes the evidence on the risk of interference from previous treatment with oral FXa inhibitors and UFH anti-Xa after heparin initiation.