A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether there is an optimal antithrombotic management for patients supported with axial-flow left ventricular assist devices (LVADs). Altogether, more than 758 papers were found using the reported search, of which 17 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. These included seven prospective and three retrospective cohort studies with a total of 538 patients with axial-flow left ventricular assist device (LVAD) (HeartMate II, Jarvik 2000, INCOR, Thoratec assist device) implanted across the world as destination therapy or bridge to transplantation. We conclude that there is a substantial alteration of the prothrombotic profile in patients with axial-flow LVADs. These abnormalities appeared to be reversible with the removal of the device and are likely to be responsible for the high incidence of non-surgical bleeding episodes reported. Warfarin seems to offer a lower thromboembolic risk compared with unfractioned heparin or low molecular weight heparin. There are reports that suggest that managing axial-flow LVAD without anticoagulation, after major bleeding complications, is possible but in all probability, these papers are subject to publication bias as poor outcomes are unlikely to have been reported. All patients with axial-flow LVAD, showed severely impaired platelet function at point of care tests. The use of warfarin (INR target 2.5), in association with aspirin at 100 mg/day, or with point-of-care tests titrated antiplatelet therapy to inhibit 70%, seems to have the best bleeding-thrombosis, and in many cases a very small dose of aspirin of 25 mg twice a day and a dose of clopidogrel of 35 mg/day, were sufficient to achieve a reduction of the maximum aggregation to less than 30%. Finally, we would like to emphasize that such recommendations are addressed only to patients with axial-flow LVAD.