Background: Deep vein thrombosis (DVT) is a common multi-factorial disease, with serious short- and long-term complications, and a potential fatal outcome. Many genes are involved in determining the inter-individual variation in traits that define the onset and progression of disease, as well as the response to treatment. No single gene is expected to have a major impact on the determination of the risk of thrombosis. Several association studies have been designed the relationship between factor XII C46T polymorphism and the risk of arterial and venous thrombosis. Some studies reported that FXII gene polymorphism is not associated with venous thrombosis, whereas other studies found an increased risk of venous thrombosis in carriers of a FXII-T variant. Patients and Method: We constructed an age-gender-ethnic-matched case-control study including 50 DVT patients and 50 healthy volunteers. C46T polymorphism of the coagulation factor XII was carried out using Allelic Discrimination Assay by Real-Time PCR System for both patients & controls, while plasma Factor XII activity was detected by one-step clotting assay. Results: FXII C46T genotyping in DVT patients revealed that 61.5% had the wild type alleles; FXII-CC, 34.6% were heterozygous harboring the FXII-CT heterotype and 3.85% were homozygous; FXII-TT homotype. Homozygous mutation of FXII gene (FXII-TT homotype) was detected in DVT patients but not in the controls. FXII activity was significantly reduced in DVT patients with mutant FXII gene. Conclusion: In conclusion, our study revealed that FXII C46T gene polymorphism was not associated with increased risk of venous thrombosis in a cohort of Egyptian DVT patients.