Intracardiac thrombi are well known complications associated with diverse cardiac diseases and venous thromboembolism. Therapeutic recommendations like thrombolysis, surgical thrombectomy, or treatment with low molecular heparin and intravenous unfractionated heparin based on small numbers of patients or retrospective case series have failed to reach a consensus. We report on the use of argatroban, a new direct thrombin inhibitor in 4 patients with intracardiac thrombi. Therapy was effective in all patients with complete resolution of thrombi. Treatment was complicated by recurrent strokes with complete neurological recovery in one patient. Therapy of intracardiac thrombi by argatroban is safe and effective. The drug requires no dosage adjustments for age, sex, or renal impairment, including in dialysis-dependent patients. Argatroban has been found to increase predictably activated partial thromboplastin time (aPTT) and activated clotting time (ACT) in a dose-dependent manner.