OBJECTIVES: To identify genetic polymorphisms in factor I fibrinogen (rs6050) and factor XI plasma thromboplastin (rs4253417) in Saudi women with recurrent spontaneous miscarriage (RSM). Furthermore, to compare the levels of clotting factors in the blood of patients and healthy controls. METHODS: The current study was conducted at the King Khalid University Hospital in Riyadh, Saudi Arabia, from September 2022 to June 2023. The study involved 100 Saudi women, 50 pregnant and 50 non-pregnant individuals, who experienced RSM. Furthermore, 100 healthy Saudi women, including 50 pregnant and 50 non-pregnant individuals, were also included as controls. TaqMan genotyping assays were used to determine single nucleotide polymorphisms in the promoter regions of the factor I and XI genes. RESULTS: A significant correlation was found between the Factor I fibrinogen genotype (rs6050 C/T) and RSM in non-pregnant Saudi women. However, no significant correlation was observed between the Factor XI polymorphism (rs4253417 C/T) and RSM. CONCLUSION: We demonstrated a significant correlation between genetic polymorphisms in factor I fibrinogen in certain genes studied and RSM. This association could be attributed to changes in fibrinogen levels, which impact the coagulation process and lead to an increase in thrombotic events, which are recognized as risk factors for miscarriage. Notably, variations in the other genes examined did not exhibit any association with the risk of RSM.