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Background: Argatroban and bivalirudin are direct thrombin inhibitors (DTIs) used for the treatment of heparin-induced thrombocytopenia (HIT). The purpose of this study was to determine whether either agent offered an advantage in efficacy and ability to remain within the targeted therapeutic anticoagulation range., Methods: This was a single-center, retrospective, observational cohort study at a large academic medical center. The primary efficacy outcome was time to therapeutic anticoagulation, defined as total number of hours to achieve 2 consecutive activated partial thromboplastin time (aPTT) values in goal range., Results: A total of 91 patients were included in the analysis. Average time to initial therapeutic anticoagulation was 4.71 hours and 9.8 hours for the argatroban and bivalirudin groups, respectively ( P < .01)., Conclusions: Argatroban may be advantageous compared to bivalirudin in achieving initial therapeutic anticoagulation goals among patients with suspected or confirmed HIT.