Acquired von Willebrand syndrome occurs in the setting of mechanical circulatory support from device-associated sheer stress, which changes the quaternary structure of high-molecular-weight von Willebrand factor multimers, exposing the cleavage site for ADAMTS-13. Once cleaved, lower-molecular-weight multimers lose their affinity for binding platelets, increasing the susceptibility to bleeding complications. Acquired von Willebrand syndrome has been described in all the currently approved continuous-flow mechanical circulatory support devices. Although theoretically the risk of von Willebrand factor multimer degradation is increased at the higher rotational speeds of axial-flow pumps, disease severity does not differ greatly between axial- and centrifugal-flow devices. Disease-specific therapies for acquired von Willebrand syndrome have not been well studied in patients supported by mechanical circulatory devices. Case reports and case series have noted beneficial effects from octreotide, doxycycline, desmopressin, or Humate-P treatment for patients with recurrent severe bleeding.