Background: Thalassemia is a hereditary disorder due to imbalance between α/β-globin chains. This leads to early hemolysis. It is of two type, α and β-thalassemia which is more sever needs lifelong follow up, treatment, by RBCs transfusion, to compensate for the drop in hemoglobin. This leads to increased iron stores andoverload, excess iron deposited in different organs and kidneys. This leads to overproduction of free radicals; that causes organ damages. Objectives:This study aimed to highlight the prevalence of renal injury in patients with β -thalassemia major, comparing subcutaneous and new oral iron chelating agents, and their effects on the renal functions. Patients and methods: This case control and observational study included a total of 60 thalassemia major patients aged between 5 and 24 years who were following up at the Hematology Outpatient Clinic, Department of Pediatrics, Cairo University Hospitals. All patients were regularly transfused and receiving regular chelation program. Patients were divided between three groups. Results: There were no significant differences between the three groups regarding glomerular filtration rate (p> 0.05), and between Deferiprone and Deferoxamine groups regarding the age, serum ferritin, serum cystatin C and urinary β₂-MG (p> 0.05). There were significant differences between Deferasirox group and both Deferiprone and Deferoxamine groups regarding serum ferritin, serum cystatin C and Urinary β₂-MG (p < 0.05). Conclusion: Younger patients who are on iron chelation therapy with deferasirox needs regular assessment of renal dysfunction markers as having relatively higher levels of serum ferritin, serum cystatin C and urinary β₂-MG.