The growing use of left ventricular assist devices as a bridge to transplant and their increased duration as destination therapy in patients successfully treated for advance heart failure unwrap a new spectrum of complications seen in long-term use of the devices. Device thrombosis remains a therapeutic dilemma, and limited data are available for the use of direct thrombin inhibitors as a treatment option. We performed a review of literature and present a series of four patients with suspected left ventricular assist device–associated thrombosis, manifesting as hemolysis, who were treated empirically with argotraban, a direct thrombin inhibitor with the ability to interact with both free and clot-bound thrombin. In this case series, we treated four patients with argatroban for suspected device thrombosis. All showed significant improvement of hemolysis according to lactate dehydrogenase measurements, and device removal was prevented in three. Bleeding complications occurred when therapy was used closer to the operative period. Argatroban can be a viable option to treat patients with hemolysis from suspected device thrombosis in patients with HeartMate II continuous-flow left ventricular assist device. Prompt attention is needed to monitor any bleeding complications.