Western part of Odisha is a region where prevalence of sickle cell disease patients is much high. The prevalence of sickle cell disease in Odisha is about 21-40%. Most of these patients suffer from different types of crises & require frequent blood transfusion. As a result they develop alloantibody resulting in hemolysis in vivo at the time of subsequent blood transfusion. Till now no study has been done in this part of Odisha regarding the prevalence of alloantibody in these patients. In general population, the prevalence of alloantibody is 5%- 8%. So, in our medical college which is a tertiary care center, a prospective study has been done to find out the prevalence of alloantibody in these groups of patients. All diagnosed Sickle Cell Disease patients by HPLC method of different age groups who have received Blood Transfusion were taken for study with their grouping & Rh typing. Then by semi automatic method, three panel antibody screening was done for each sample & DAT was also done for all cases. Out of 90 no. of Sickle Cell Disease patient’s alloantibody was detected in 11 samples. Direct Antiglobulin test was positive in all these cases. In Sickle Cell Disease, who received Blood transfusion, alloantibody formation in these patients is a probability in some cases leading to Delayed Hemolytic Transfusion Reactions. In these patients corresponding antigen negative blood transfusion should be given.