Unfractionated heparin (UFH) is required in children on extracorporeal life support (ECLS) to maintain circuit patency. When high-dose UFH is inadequate to maintain an anticoagulant effect, the addition of antithrombin concentrate (ATC) is considered. The objective of this study was to review clinical experience giving 1,000 units (U) of ATC to patients on ECLS and UFH anticoagulation. Specifically, antithrombin (AT) levels pre- and post-administration of high-dose ATC, estimation of the efficacy of high-dose ATC administration as measured by the level of anticoagulation, and the incidence of adverse effects were determined. A retrospective chart review of all infants and children on ECLS who received ATC between June 2008 and May 2011 at Stollery Children's Hospital, Edmonton, Canada, was performed. A total of 78 doses of ATC were administered to 36 patients with a median age of 2.9 months (interquartile range, 0.6-12.6) on ECLS. Mean dose of ATC was 241 U/kg (95% confidence interval, 199-283). Mean AT level pre- and post-administration was 0.40 and 0.93 U/ml, respectively. Mean anti-Xa level pre- and post-AT administration was 0.23 and 0.41 U/ml, respectively. There were no associated acute adverse events. The administration of high-dose ATC decreases UFH dose requirements.