Empowering caregivers’ adherence to therapeutic regimen after children kidney transplantation play role in graft survival and improving quality of life of children and their families. Aim of the study: To evaluate the effect of empowerment program on caregivers' adherence to therapeutic regimen of their children after kidney transplantation. Design: Quasi-experimental design. Sample: A convenient sample consisted of 06 caregivers of children aged ranges from 6-18 years divided into two groups; study and control. Setting: The study was carried out at the kidney transplantation outpatient clinic at Al- Monira Pediatric Hospital which affiliated to Cairo-University Hospitals. Tools for data collection: Data collected using five tools including structured interview questionnaire, caregivers' adherence to therapeutic regimen and its related knowledge, observational checklist (oral medications, hand wash, oral care, skin care, and care of fever), laboratory investigations record and self-efficacy scale. Results: The mean age of children among study and control groups were thirteen years and more, the majority of caregivers were children’s mothers, less than three fifths of children had less than two years duration after KT, all children were hospitalized after KT due to abnormal laboratory investigations. After the program the caregivers total mean scores of knowledge’s, practices, self-efficacy, and adherence among the study group improved in posttest and follow-up than before. Also, significant positive correlation was detected between them Conclusion: The current study concluded that, the empowerment program improves significantly the total scores of caregivers’ knowledge, practices, self-efficacy and the adherence to therapeutic regimen. Recommendation: It was recommended that to integrate the empowerment program for caregivers to the routine care of children post KT.