Acquired von Willebrand disease increases bleeding risk in patients implanted with a continuous-flow left ventricular assist device. Lower aspirin (ASA) doses decrease the risk of bleeding without an increased risk of embolic events. No published studies in the United States have compared the incidence of bleeding and thrombotic events between antithrombotic regimens with and without ASA. A single-center, retrospective analysis was conducted of adult patients implanted with a HeartMate II (HM II). Patients received warfarin and ASA 81 mg daily or warfarin alone. The primary end-point was a composite of death, bleeding events, and thrombotic events from the date of HM II implantation to first event or 18 months. Secondary end-points included the individual components of the primary end-point and the proportion of patients alive with HM II or transplanted. The Wilcoxon rank sum test and Fisher’s exact test were used for statistical analysis. Of the 76 patients meeting inclusion criteria, 44 received warfarin and ASA and 32 received warfarin alone. Baseline characteristics were similar between groups. Warfarin alone was not associated with an increased risk of the primary composite outcome (53 vs. 59%, respectively, p = 0.64). No significant difference was observed in any bleeding event (34 vs. 43%, respectively, p = 0.48) nor any thrombotic event (9 vs. 11%, respectively, p = 1.00) with warfarin alone compared with warfarin and ASA. Elimination of antiplatelet therapy from the HM II antithrombotic regimen was associated with no significant difference in the composite outcome of bleeding events, thrombotic events, or death, nor the individual components of each end-point.