Bleeding complications are frequently observed in patients undergoing extracorporeal membrane oxygenation and are associated with increased mortality. Due to the complex mechanisms, managing bleeding during ECMO remains a challenge. Acquired von Willebrand syndrome (AVWS) in ECMO highlights a potentially reduced affinity of von Willebrand factor (vWF) for binding to platelets and collagen in response to vascular damage, thus contributing to increased bleeding in ECMO patients. Conventional coagulation parameters are incomplete predictors for bleeding in ECMO patients, whereas AVWS is often overlooked due to the absence of vWF evaluation in the coagulation profile. Therefore, clinical physicians should evaluate AVWS in patients experiencing bleeding complications during ECMO support.