Background: Pregnancy is sufficiently considered an important risk factor for thromboembolic events. We aimed to determine the prevalence of factor V Leiden (FVL) and prothrombin gene 20210A mutations in patients with miscarriages and to correlate these results with normal and abnormal karyotypes. Methods: A retrospective study was carried out in 247 women with a history of miscarriages. These samples were karyotyped, and the DNA was extracted (chorionic villi) and genotyped for FVL and prothrombin gene polymorphism. Results: Polymorphism frequency was compared among different groups. FLV showed significant levels in the normal cytogenetic groups in two comparisons: normal abortion (NA) versus abnormal abortion (AA) (P = 0.08) and normal recurrent abortion (NRA) versus AA (P = 0.048). The presence or absence of at least one polymorphism was evaluated. The frequency of G20210A prothrombin gene polymorphism was higher in NA than in AA: NA versus AA (P = 0.014), NRA versus AA (P = 0.018) and AA versus NRA (P = 0.01). Conclusions: The FVL showed probable importance in the genesis of abortions due to its greater frequency of normal karyotype miscarriage. Once presence of both polymorphisms was significantly higher in normal karyotype miscarriage than in abnormal, we can infer that the alterations are associated with the pathophysiology of abortions. J Clin Gynecol Obstet. 2016;5(3):85-91 doi: http://dx.doi.org/10.14740/jcgo412e