Anticoagulation for extracorporeal life support (ECLS) is routinely achieved using heparin, which can be difficult in patients suspected of having heparin-induced thrombocytopenia. We describe a case series of five patients in which we used argatroban, a direct thrombin inhibitor, as an alternative to heparin for systemic anticoagulation during ECLS in patients suspected to have heparin-induced thrombocytopenia. Argatroban was used to achieve target systemic anticoagulation for activate clotting times between 210 and 230. Duration of argatroban use while on ECLS ranged from 6 to 184 hours. Argatroban dosage ranged from 0.2 to 3.5 μg/kg/min. Activated clotting times showed good agreement with aPTT. In conclusion, we illustrate that argatroban is a reasonable alternative to heparin anticoagulation for patients requiring ECLS.