This study examines the use of argatroban as an alternative to unfractionated heparin (UFH) for anticoagulation during veno-venous ECMO in COVID-19 patients with heparin-associated thrombocytopenia (HIT). Data from 40 patients revealed a lower incidence of bleeding with argatroban compared to UFH, particularly at tracheal stoma sites. Platelet counts showed better preservation with argatroban, despite comparable efficacy in preventing thrombotic events. Argatroban offers a safer alternative for HIT cases in ECMO.