BACKGROUND: Unexplained recurrent miscarriage (RM) is still an unsolved reproductive health problem. Inherited thrombophilias have been one of the causes. Mutation in genes encoding coagulation proteins, including prothrombin (PT G20210A) and methylenetetrahydrofolate reductase (MTHFR) genes, increase tendency for venous thromboembolism. This study aimed to evaluate association between polymorphisms in prothrombine and MTHFR genes with RM. We also evaluated association between protein C (PC), protein S (PS), antithrombin III (ATIII), and homocystiene with RM. MATERIALS AND METHODS: We conducted a case-control study on women with history of miscarriages and healthy controls. Genetic analysis was done using (TaqMan) polymerase chain reaction (PCR) technique and the other tests were performed to check general health indications and thrombophilia markers. RESULTS: In this study, 195 RM group (group I) participants and 90 healthy controls (group II), PC, PS, ATIII deficiency and Hyperhomocysteinemia were in 7.2, 65.6, 9.2, 10.8% of group I respectively, but was 1.1, 7.8, 2.2, 2.2% of group II. PT G20210A showed two in group I were A/G, no A/G in group II, and no AA carrier in the either group. G allele was observed in 99.5% of the group I and 100% of the group II, while A allele was detected in 0.5% of group I. MTHFR C677T gene showed C/T mutation in 33.3% of group I and 32.2% of group II, while T/T mutation was detected in 12.8% of group I and 8.9% of the group II. C allele was found in 70.5% of group I and 75% of group II, while T allele was found in 29.5% of group I and 25% of group II (P=0.269). CONCLUSION: PT G20210A and MTHFR C677T gene mutations are not correlated with RM in the Egyptian population. However, Egyptian women with RM are strongly associated with hyperhomocysteinemia, PC, PS, and ATIII deficiencies (registration number: NCT03209063).