To prevent thromboembolic events associated with heparin-induced thrombocytopenia (HIT), patients usually are treated with argatroban, lepirudin, and bivalirudin. Here, we conducted a meta-analysis of studies to comparing the treatment of HIT with the following direct thrombin inhibitor: argatroban versus lepirudin and argatroban versus bivalirudin. We systematically searched PubMed, Embase, and Cochrane Library database for relevant studies. The clinical outcomes were thromboembolic complication and bleeding. A total of 589 articles were found and 9 of which were finally included in this meta-analysis. There were no significantly differences of thromboembolic complication between argatroban and hirudin analogues (lepirudin and bivalirudin) in the treatment of HIT (lepirudin: RR = 0.773, 95% CI = 0.449-1.331, P = 0.353; bivalirudin: RR = 0.768, 95% CI = 0.386-1.527, P = 0.452). Moreover, the incidence of clinical bleeding of argatroban was similar to hirudin analogues (lepirudin: RR = 0.755, 95% CI = 0.531-1.073, P = 0.117; bivalirudin: RR = 0.995, 95% CI = 0.673-1.472, P = 0.981). Current evidences show that argatroban has the similar effectiveness and safety with lepirudin and bivalirudin for defending against HIT.