OBJECTIVE: The purpose of this study was to investigate the possible role of inherited and acquired thrombophilia in women with unexplained abortions and intrauterine fetal death. STUDY DESIGN: We included 75 women with greater than or equal to 1 unexplained fetal loss, and 75 control subjects with at least 1 healthy term infant and without gestational complications. All of these women were tested for mutations of factor V Leiden, methylenetetrahydrofolate reductase, and prothrombin gene; deficiencies of antithrombin-III, protein C, and protein S; and the presence of anti phospholipid antibodies and fasting homocysteine concentration. A placental histologic study was also carried out. RESULTS: Thirty-five percent of the 75 patients had thrombophilia (control subjects, 16%; P = .008; odds ratio, 2.78). This prevalence was more prominent in second and third trimesters (P = .0002; odds ratio, 6.3), and the presence of combined genetic defects was associated with intrauterine fetal death (P = .04; odds ratio, 12; 95% Cl, 1.44-102). When we analyzed the overall gestations of the patients, we observed an increase of intrauterine fetal death in patients with thrombophilia (P = .01) and early pregnancy loss in patients without thrombophilia (P = .02). The analysis of the correlation between extensive placental infarctions and thrombophilic defects rendered values in the boundaries of significance (P = .05). CONCLUSION: The significant high prevalence of biologic causes in patients with late fetal loss suggests that a study of thrombophilia should be carried out, together with an assessment of a preventive treatment.