Background: The thalassemias are hereditary hemolytic anemias characterized by reduced or absent synthesis of one or more of globin chains of hemoglobin leading to globin chain imbalance. The most important forms of thalassemia result from autosomal mutant genes that reduce the rate of synthesis of α and β chains of hemoglobin (Hb) A, leading to α and β thalassemias respectively. In Egypt, β-thalassemia is the commonest form of chronic hemolytic anemia among Egyptian children. Formation of alloantibodies resulting in clinical hemolysis, and difficulty in cross-matching blood, and shortening of the duration of RBC's survival. Objective: To detect the presence of alloantibodies in regularly transfused beta-thalassemic patients and to identify type of these antibodies. Patients and Methods: This is a cross sectional study on one hundred transfusion dependent B thalassemic patients for presence of alloantibodies.  The study included children with thalassemia who attended to outpatient clinic at Zagazig University Hospital aged from 1 to 16 from June 2019 to June 2020. Results: Alloantibody was negative in 82% of cases, and positive in 18%. Of positive cases 61.1% had anti E, 16.7% non-specific, 11.1% anti E and anti-JKB and 11.1% anti E and anti C. There was no statistically significant difference between patients with negative and positive alloantibodies as regard sex, age or consanguinity, Conclusion: Alloimmunization to red blood cell antigens are frequent finding and quite relevant among Egyptian transfusion-dependent thalassemic patients. The most frequent antibodies detected were anti-E. The majority of alloantibodies detected in the current study were clinically significant.