Study of the factors responsible for red cell alloimmunization can help in adopting appropriate strategy to minimize alloimmunization. However data for thalassemia patients from our region is limited. Therefore, a study was conducted to find out the frequency and the factors associated with red cell allo and autoimmunization in thalassemia patients at our center so as to enable us to take appropriate action to reduce alloimmunization. Clinical, demographic, allo and autoantibody and transfusion records of 280 thalassemia patients at our hospital were studied. Patients with and without alloantibodies were compared to find significant differences for age, gender, race, age at start of regular transfusions and splenectomy. Red cell antigen frequencies in thalassemia patients and published antigen frequencies in blood donors from the same center were compared to look antigen differences as a risk factor for alloimmunization. Twenty four thalassemia patients (8.6 %) developed 28 clinically significant alloantibodies. 18 (65 %) of the alloantibodies were of Rh system. The three most common antibodies detected was anti E (11, 39.3 %) followed by anti K (6, 21.4 %) and anti c (10.8 %). Five (1.8 %) of the 280 patients developed autoantibodies. Patient age was found to be significantly higher in alloimmunized patients than in non alloimmunized patients. Red cell antigen frequencies between blood donor and recipient populations were found to be homogenous for most of the relevant RBC antigens. The frequency of red cell alloimmunization in thalassemia patients from our center is moderate. In this setting of red cell phenotype concordant donor-recipient population requirement of extended phenotype matched transfusions may not be cost effective.