Background Accumulating evidence suggests that inherited thrombophilia may be implicated in the occurrence of recurrent pregnancy loss (RPL) via adversely affecting the placental vascular function. We aimed to investigate the possible association of MTHFR (rs1801133 and rs1801131), FV rs6025, FII rs1799963 and PAI-1 rs1799889 polymorphisms with increased risk of RPL. Material and methods A total of 320 women with a history of at least two consecutive miscarriages and 100 healthy controls were included in the study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used for genotyping of the studied single nucleotide polymorphisms (SNPs). Using logistic regression analysis, odds ratio (OR) and 95% confidence interval (95% CI) were calculated to determine the association between the SNPs and RPL, under co-dominant, dominant and recessive inheritance models. Results The results showed that rs1801133 (OR: 2.158; 95% CI: 1.310-3.553; P = 0.002) was significantly associated with increased risk of RPL, under dominant inheritance model. We also found that rs1799889 was related to a high risk of RPL in co-dominant, dominant and recessive inheritance models. MTHFR rs1801133 T and PAI-1 rs1799889 4G alleles were found to be significantly more prevalent in RPL patients compared to healthy controls (P < 0.05). Conclusion These data provide strong evidence that rs1801133 and rs1799889 SNPs were significantly associated with increased risk of RPL, suggesting their potential role in RPL pathogenesis. [ABSTRACT FROM AUTHOR]