Background and objectives:Warfarin is one of the most widely used anticoagulants, yet inter-individual differences in drugresponse, a narrow therapeutic range, and a high risk of bleeding or stroke complicate its use. Weaimed to determine allele frequency and genotype distribution of VKORC1 1173 C>T,CYP2C9*2 and CYP2C9*3 variant polymorphisms in Egyptian population. Also to evaluate theinfluence of these variant polymorphisms on the inter-individual differences in warfarin dosage.Methods:154 unrelated healthy adult subjects and 46 warfarin-treated patients were included. SYBERGreen-based real time PCR assay was used for studying VKORC1 (C1173T) and CYP2C9*3polymorphisms. For the detection of CYP2C9*2 allele the mutagenic separated PCR assay wasused.Results:VKORC1 genotypes frequencies were 11, 24 and 65 % for CC, CT and TT respectively.CYP2C9 haplotypes prevalence’s’ were *1/*1 (81%), *1/*2 (3.3%), *1/*3 (9.7%), *2/*2 (4.5%),*2/*3 and *3/*3 (0.65%). The VKORC1 TT and CYP2C9*2/*2 were associated with asignificantly lower warfarin dose. Neither *2/*3 nor *3/*3 haplotype was detected amongpatients. VKORC1 and CYP2C9 accounted for 31.7% and 15.6% of warfarin dose variability,respectively, and together with clinical factors explained 61.3% of total variability.Conclusion:VKORC1-TT and CYP2C9 *1/*1 are the most prevalent genotypes among the Egyptianpopulation. More than half of the warfarin treated patients had VKORC1-TT genotype thatrequired lower warfarin dose. These genetic factors along with age, sex and weight attributed for61.3% of warfarin dose variability. A model that included these covariates was developed forwarfarin dosing to achieve INR value of 2-3 in Egyptian patients.