Current literature suggests that acquired von Willebrand syndrome associated with Wilms tumor (AVWS-WT) occurs infrequently and usually has little clinical significance. Treatment strategies are thus poorly defined. We describe two patients with AVWS-WT and profuse bleeding who required intensive multimodal therapy, including aggressive blood component and factor replacement and plasmapheresis. They achieved adequate surgical hemostasis only after the renal vessels were ligated, with resolution of the coagulopathy upon tumor removal. Our experience suggests that AVWS-WT is not always benign. A careful bleeding history should always be obtained in patients with suspected renal tumors for consideration of pre-operative screening for AVWS.