This study aimed at Assessment of Factor V Leiden, Prothrombin gene mutation and Methylenetetrahydrofolate reductase activity in thalassemic patients and its role in thromboembolic manifestation. Study was conducted on 40 Thalassemic patients following up at pediatric Hematology Clinic, New Children Hospital, Cairo University. Results show that 2 (5%) patients had thromboembolic manifestation and that genotypes of factor V Leiden G1691A were 87.5% wild (GG) genotype, 12.5% heterozygote genotype (GA) and 0% homozygous genotype (AA) and A allele frequency was 6.25. Regarding Prothrombin G20210A genotypes were 97.5 wild (GG) genotype, 2.5% heterozygote genotype (GA) and 0% homozygous genotype (AA) and “A allele” frequency was 1.25. Regarding MTHFR C677T genotypes were 42.5% wild (CC) genotype, 50.0% heterozygote genotype (CT) and 7.5% homozygote genotype (TT) and “T “allele frequency was 32.5. Conclusion: Heterozygous MTHFR gene mutation is a common finding in Thalassemic patients but rarely associated serious thromboembolic events