Inherited thrombophilia has been implicated as a possible cause of recurrent pregnancy loss. Although numerous studies are available in literature, thrombophilia rate seems to vary fromstudy to another. The aim of our study was to determine the frequency of FII Prothrombin(G20210A), Factor V Leiden (G1691A), as well as methyl tetrahydrofolate reductase (MTHFR C677T) polymorphisms, protein C, protein S and antithrombin III deficiency in a series of patients with unexplained RPL compared to control. Patients and Methods: 100 patients of unexplained RPL and 43 age-matched healthy controls were investigated for inherited thrombophilia. Results: MTHFR and Factor V Leiden were the commonest gene defects among cases studied (63%, 60% respectively) and control groups (41.9%, 41.9% respectively) (p = 0.019, p = 0.046 respectively). The least common deficiencies were protein S and protein C deficiency in cases (3%, 2% respectively) as well as in controls (1%, 0% respectively). 4 cases were homozygous for MTHFR and 2 cases homozygous for Factor V Leiden mutation. Odds ratio for MTHFR and Factor V mutation was 2.36 and 2.08 respectively (CI 95%). Combined defects were seen in cases and controls (p < 0.05). Conclusion: Our study found an association between MTHFR and Factor V Leiden mutations in patients with unexplained RPL among Egyptian women. Further studies are needed to define the management of genetic thrombophilia in cases of recurrent pregnancy loss.