The extent of hematologic effects of the new continuous flow left ventricular assist devices (CF-LVAD) has not been studied. Recent clinical studies have demonstrated that hemolysis and thrombosis are not common during CF-LVAD support, however, the incidence of bleeding remains a concern. The rate of postoperative bleeding is similar to that of the prior generation pulsatile LVAD, but gastrointestinal bleeding due to angiodysplasia and arteriovenous malformations is more common and appears to be related to the blood flow rheology of these devices. New evidence suggests that acquired von Willebrand’s disease develops in some patients due to the reduction in high molecular weight (HMW) multimers of von Willebrand’s factor (vWF). Similar to acquired von Willebrand’s disease seen in patients with aortic stenosis, the shear stress of the CF-LVAD may cause proteolysis of the HMW multimers of vWF. In addition to acquired von Willebrand’s disease, there is activation of the fibrinolytic system and a loss of platelet numbers and function during CF-LVAD support. The hematologic responses during CF-LVAD support are constantly changing, and antiplatelet therapy may need to be adjusted accordingly. Considerable research is needed to better define the complex hematologic effects during CF-LVAD support. Screening of patients for angiodysplasia and von Willebrand’s disease before CF-LVAD implant may allow for effective preemptive treatment. Because bleeding causes significant morbidity for this population, more effective treatment strategies need to be developed.