Objective This study aims to analyze the clinical and laboratory characteristics of M protein-associated acquired von Willebrand syndrome (AVWS), and to improve clinical recognition and diagnostic capability. Methods Four patients with M protein-associated AVWS identified at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, between October 2024 and April 2026 were consecutively enrolled and retrospectively reviewed. Three patients presented with unexplained bleeding, whereas one was found to have abnormal hemostatic laboratory results during inpatient scree-ning. After von Willebrand factor （VWF)-related testing and differential evaluation for inherited von Willebrand disease(VWD) and other bleeding disorders, serum protein electrophoresis and immunofixation electrophoresis were subsequently performed to detect M protein. Results Among the four patients, three were male and one was female, with ages ranging from 38 to 71 years. None had a long-standing history of abnormal bleeding or a family history of bleeding. Two patients were diagnosed with Waldenström macroglobulinemia (WM) based on bone marrow pathology and molecular pathology fin-dings, whereas two were clinically suspected of having monoclonal gammopathy of undetermined significance (MGUS) wi-thout undergoing bone marrow examination. VWF antigen (VWF:Ag), VWF activity (VWF:Act), and factor Ⅷ coagulant activity (FⅧ:C) were decreased in all four patients. The VWF:Act/VWF:Ag ratio was <0.60 in three patients, whereas the ratio was 0.74 in the remaining patient. Qualitative analysis of VWF multimers showed a marked reduction in high-molecular-weight VWF multimer bands in all four patients compared with normal pooled plasma. Conclusions The main diagnostic features of M protein-associated AVWS include adult onset, absence of a family history of abnormal bleeding, coexisting monoclonal immunoglobulin abnormalities, a disproportionate reduction in VWF activity relative to VWF antigen, and a reduction in high-molecular-weight VWF multimers. In patients with unexplained bleeding or abnormal VWF-related parameters, serum protein electrophoresis, immunofixation electrophoresis, and M protein quantification should be further performed to avoid missed diagnosis and misdiagnosis.