The purpose of this study was to examine the relationship among adverse pregnancy outcome, the presence of thrombotic lesions in the placenta, and the frequency and type of laboratory abnormalities consistent with the presence of a thrombophilic state. A retrospective cohort study was designed to determine the frequency of laboratory abnormalities consistent with thrombophilia among patients with thrombotic lesions of the placenta and adverse pregnancy outcome. The workup for a thrombophilic state included anticardiolipin antibodies, lupus anticoagulant, protein C and antithrombin III activities, protein S total and free, activated protein C resistance ratio, and Factor V Leiden mutation. Thrombotic lesions were identified by histopathologic examination of the placenta. Thirteen patients met the study criteria over an 11-month period. Seven patients were heterozygous for Factor V Leiden mutation (53.8%). Protein S deficiency was found in three cases (23.0%), and no hemostatic abnormality was detected in three cases (23.0%). Mothers with an adverse pregnancy outcome and thrombotic lesions of the placenta often have laboratory abnormalities indicative of a thrombophilic state. We propose that thrombophilia leading to thrombosis in the maternal and/or fetal circulations is a significant mechanism of disease during pregnancy.