Background: Thalassemia is a chronic disease that has a significant impact on the health of many children. It necessitates regular medical care from physicians or other health experts, as well as the usage of medicines on a regular basis. Unfortunately, repeated hospitalization, intensive medical care, and home management are all required. Aim: Assess the compliance of children with thalassemia to their therapeutic regimen. Method: A descriptive design was used to accomplish this study that conducted at Out Patient Clinic in Hematological Diseases Unit at Alexandria University Children's Hospital, A convenient sample of 100 children with thalassemia and their mothers using Compliance of Children with Thalassemia to their Therapeutic Regimen Structured Interview Schedule of two parts was utilized, Part (I): Medical History of Children and Part (II): Children with Thalassemia Compliance to Their Therapeutic Regimen. Results: It was obvious that 98.0% of studied children were always in compliance with their therapeutic regimen, while 2.0% of them were sometimes in compliance with their therapeutic regimen. Conclusion: Based on the findings of the present study, it is concluded that the majority of children with thalassemia were always complying with their therapeutic regimen in this study. Meanwhile, minority of them were always complying with their nutrition.