Background:Maternal thrombophilia has been identified as a risk factor for recurrent pregnancy loss (RPL). The aim of this study was to investigate the association between prothrombin G20210A and factor V Leiden (FVL) polymorphisms in women with RPL and a control group of parous women in Isfahan province of Iran.Methods:We studied 250 women with idiopathic RPL and 116 control cases. Prothrombin and FVL different genotypes were determined using polymerase chain reaction and reverse hybridization technique.Results:The frequencies of heterozygous mutation prothrombin G20210A were 6% and 0.9%, respectively (P = 0.025), in cases compared to the control group. The frequencies of homozygous mutation prothrombin G20210A were 0.4% and 0%, respectively, in cases compared to controls (P = 0.02). The prothrombin mutation was significantly higher in cases compared to the control group (odds ratio 8.81; 95% confidence interval: 1.16–66.62). There was no significant difference between the FVL mutation and pregnancy loss.Conclusions:The results indicated a significant higher frequency of prothrombin G20210A in women with RPL in comparison with controls. Our data suggest that the prothrombin G20210A mutation, but not the FVL mutation, may be an unrecognized cause of RPL in our population.