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Heparin-induced thrombocytopenia requires immediate alternative anticoagulation to prevent or treat thrombo-embolic complications. Argatroban was approved based on multiple-center studies from the 1990s, but subsequent changes in prevailing awareness, diagnostic testing and therapeutic strategies for heparin-induced thrombocytopenia might affect results of argatroban therapy. Charts were retrospectively reviewed from patients administered argatroban for suspected heparin-induced thrombocytopenia over 22 months at a single large university hospital. Twenty-seven patients, most in intensive care units, received a median 0.5 μg/kg/min argatroban over a median 5.5 days. Patients had isolated heparin-induced thrombocytopenia (n = 10), had heparin-induced thrombocytopenia with thrombosis (n = 9), or lacked active heparin-induced thrombocytopenia (n = 8) on final analysis. New thromboses (14.8%), progression of preexisting thromboses (0%), amputation secondary to heparin-induced thrombocytopenia (0%), death (22.2%), bleeding requiring transfusion (3.7%), and any bleeding (22.2%) compared favorably with older multiple-center reports. Deaths occurred mainly with preexisting multiple-organ failure. In contemporary “real world” use, argatroban provides safe and effective anticoagulation, strengthening the mandate to initiate alternative anticoagulation whenever heparin-induced thrombocytopenia appears likely.