During normal pregnancy, the pro-coagulant activity is increased, while the anticoagulant activity is reduced, resulting in a prothrombotic environment that predisposes toward venous thromboembolism (VTE). VTE occurs frequently in pregnant women and is a leading cause of maternal morbidity and mortality. Hemostatic abnormalities were examined in 14 pregnant women with deep vein thrombosis (DVT). We studied five families with congenital antithrombin (AT) deficiency and two families with congenital protein C (PC) deficiency. One woman with PC deficiency showed protein S (PS) Tokushima. The AT activity levels were significantly lower at the onset of DVT in the pregnant women than during the stable state. The PS activity and antigen levels were also significantly lower at the onset of DVT. In the patients with congenital AT deficiency, AT activity was significantly lower in the stable state and decreased further at the onset of DVT. Although AT levels were normal before pregnancy, they subsequently decreased and in two cases the patients required the administration of AT after pregnancy. Gene analysis revealed one family with AT Budapest, one family with AT Toyama, and three families with AT Glasgow. Additionally, there was one family with PC Tochigi and one family with combined heterozygous PC deficiency and PS Tokushima. In conclusion, the deficiency of natural anticoagulants, especially AT, is an important cause of pregnancy-related VTE.