Objective: The aim of our study was to investigate the prevalence of factor V Leiden and its relation with RPL in a group of Syrian women. Materials and Methods: The study group included 35 women with a history of recurrent pregnancy loss (two or more abortions before 20th week of gestation) were referred to Orient hospital for obstetrics, gynecology and assisted reproduction, Damascus, Syria, for investigation between December 2005 and July 2006. All women with known causes of pregnancy loss after convenient investigations were excluded. The control group included 45 healthy women from the same ethnic background, who had at least one successful pregnancy, and none of them had a history of fetal loss or complicated pregnancy. FVL mutation was screened by Real-time PCR method. Results: The results show that 10 women out of 35 with RPL and 4 women out of 45 controls had FVL mutation (28.6 versus 8.9 %,P=0.022, Odds ratio 4.1, 95% CI: 1.16-14.4). From the 25 women who were primary RPL, eight patients had the factor V Leiden (32 versus 8.9%, P=0.014, OR: 4.8, 95%CI: 1.2, 18.17). From the 10 women who were secondary RPL, two patients had the factor V Leiden (20 versus 8.9%, P=0.30, OR: 2.5, 95% CI: 0.4-16.4). All patients and controls carrying the factor V Leiden were heterozygote. Conclusion: Our results revealed that the prevalence of FVL was significantly higher in women with RPL in comparison with controls, particularly in the subgroup with primary RPL, and there is an association between factor V Leiden mutation and recurrent pregnancy loss.