During extracorporeal membrane oxygenation (ECMO) support, the high shear stress in the ECMO circuit results in increased proteolysis of von Willebrand Factor (VWF), loss of VWF high molecular weight (HMW) multimers, and impaired ability to bind to platelets and collagen. These structural changes in VWF are consistent with acquired von Willebrand syndrome (AVWS) type 2A and may contribute to the bleeding diathesis frequently observed in ECMO patients. We performed a systematic review of all clinical studies evaluating the prevalence and associated outcomes of AVWS in ECMO patients. Our findings suggest that almost all ECMO patients develop partial or complete loss of VWF HMW multimers within a few hours of device implantation. The AVWS persists as long as the patient is supported by ECMO. Weaning from ECMO rapidly and completely resolves the AVWS. Nevertheless, few studies have reported bleeding outcomes in ECMO patients with AVWS, and the extent to which AVWS contributes to the bleeding diathesis during ECMO support cannot be answered by current evidence. Data supporting the use of VWF concentrates to prevent bleeding complications in ECMO patients remain limited.