Red blood cells (RBC) are the most commonly transfused blood product globally. Approximately 85 million RBC units/year are transfused to treat hematological conditions like severe anemia, leukemia, stem cell transplants, severe hemorrhage, and sickle cell disease (SCD).1 While these transfusions are essential, patients requiring repetitive transfusion are at a high risk of alloimmunization that can lead to delayed or acute hemolytic transfusion reactions (HTRs), fetal anemia, and complications during pregnancy.2 Red blood cells (RBCs), or erythrocytes, are the cells in charge of delivering oxygen to the body tissues, and carbon dioxide from the body tissues towards the lungs.The International Society of Blood Transfusion (ISBT) Working Party for Red Cell Immunogenetics and Blood Group Terminology (ISBT WP) maintains an official record of all currently recognized blood group systems. As on November 2023 there are currently 45 recognized blood group systems containing 362 red cell antigens. The 45 systems are genetically determined by 50 genes. These antigens are either sugars or proteins, and they are attached to various components in the red blood cell membrane and  are often ignored by the immune system. However, when patients receive blood transfusions, their immune systems will attack any donor red blood cells that contain antigens that differ from their self-antigens. Therefore, ensuring that the antigens of transfused red blood cells match those of the patient’s red blood cells is essential for a safe blood transfusion.3The current blood transfusion policy is the transfusion of ABO, D-matched red blood cells (RBC), and in many countries it is advised to give women in childbearing age cE-matched and K– blood. Only in patients who recurrently need RBC or platelet (PLT) transfusions is preferentially more widely matched blood given. Therefore, in approximately 5 percent of transfused patients, alloantibodies are induced.4,5These antibodies may result in a compatible crossmatch with an ABO group-specific random donor unit showing heterozygous expression of that antigen. Subsequent exposure to donor RBCs having these antigens usually leads to a brisk anamnestic antibody response within 48–72 h, which reaches its peak at 7–10 days post-transfusion. These antibodies are typically IgG, and can result in a delayed hemolytic transfusion reaction.6 Alloimmunization to RBC antigens is stimulated not only by transfusion but also through feto-maternal hemorrhage during pregnancy.7 The incidence of RBC alloantibodies varies in different patient populations.8–10.In this Scenerio Regional Testing Centre in the Department of Transfusion Medicine, Madras Medical College, has done 450 samples of alloimmunization in which 55-60% alloimmunization is  present among the transfusion dependent patients.