In 16 cases, acquired von Willebrand syndrome (AvWS) and hypothyroidism have been described that occur with each other: 15 women and one man, at a mean age of 32 years, range, 13 to 82 years of age. Activated partial thromboplastin time (APTT) was normal in six patients, and five patients had factor VIII concentration (factor VIIIc) levels in excess of 60%. The bleeding time was prolonged in nine of 13 evaluable patients. Activated partial thromboplastin time was prolonged in seven patients, and five of these had factor VIIIc levels between 18 and 45%, with two patients having levels in excess of 60%. A deficiency of other coagulation factors, including factor VII, V, IX, and X, caused by a generalized diminution in protein synthesis in hypothyroidism, may have contributed to the prolongation of the APTT. The AvWS was very likely type 1 in all cases because of a normal von Willebrand factor antigen/ristocetin cofactor (vWF Ag/RCF) ratio. Acquired von Willebrand syndrome was documented via cross immunoelectrophoresis in three patients and via multimeric analysis of vWF in six patients. A definite diagnosis of AvWS type I has to be confirmed by a normal response to 1-desamino-8-D-arginine vasopressin (DDAVP). Treatment of hypothyroidism with thyroxine was associated with the disappearance of the AvWS and the bleeding diathesis. Decreased factor VIIIc, vWF Ag and vWF RCF levels (50%, 33%, and 36% respectively) before thyroxine treatment increased to normal values (97%, 93%, and 107% respectively) after treatment. The absence of bleeding, or mild bleeding, symptoms, in relation to those more commonly recognized with hypothyroidism, has led to the complication of acquired vWF deficiency being underdiagnosed. Acquired von Willebrand syndrome type I should be considered whenever hypothyroidism is diagnosed and thyroid biopsy or surgery is contemplated. The complete relief of AvWS via treatment of hypothyroidism with thyroxine is the final proof of this association and causal relationship.