Background:Tacrolimus is an important immune suppressant medication utilized following transplantation of organ. It is primarily metabolized by cytochrome P450, family 3, subfamily A (CYP3A) enzymes, with significant individual variances in metabolism. Aim of the work:This study aimedto examine the effect of the polymorphism of the CYP3A5 rs776746 gene on the blood concentration and tacrolimus dose of recipients and donors, as well as their role in the individualization of tacrolimus dose in Egyptian liver transplant recipients. Patients and methods:The investigation comprised 25 liver transplant recipients and their respective donors. Polymorphism of CYP3A5 gene was assessed in all individuals using RT-PCR. For recipients, tacrolimus trough levels were determined, and the weight-adjusted tacrolimus concentration and dosage -to-dose ratio (C/D) have been determined. Results: The current investigation demonstrated that recipients with at least one allele of the CYP3A5 3*1 and 1*1 genotypes demanded a larger dosage of tacrolimus compared to those with the 3*3 genotype, but this variance wasn't statistically significant. Recipients of donors with CYP3A5 3*1 and 1*1 genotypes demanded elevated doses of tacrolimus to attain the target trough levels, resulting in a reduced ratio of C/D, in contrast to recipients of donors with the 3*3 genotype, with a statistically significant variance observed during the initial month following transplant. Conclusion:The investigation found that the CYP3A5 genotype of recipients and grafts demands a greater tacrolimus dose than the 3*3 genotype, and the graft genotype significantly impacts the tacrolimus dose & C/D ratio.