Background and objectives: Distribution of blood group antigen varies among different races. It is important to know the distribution of these antigens so as to provide a donor database that aid in providing compatible blood units for patients with multiple alloantibodies. The present study was conducted to determine the distribution of clinically significant minor blood group antigens amongst the South Indian blood donors. Materials and methods: Blood samples were collected from healthy regular repeat voluntary blood donors of same ethnicity attending a tertiary care hospital in South Kerala. Clinically significant blood antigens of the ABO, Rh (D, C, c, E, and e), Kell, Duffy and Kidd blood group systems were determined. The ABO and Rh(D) grouping were performed by tube technique using monoclonal antisera. Column agglutination technique was used to phenotype Rh, Kell, Duffy and Kidd antigens. Results: Total 200 healthy repeat voluntary blood donors were enrolled in the study. Out of 200 donors, 92% were RhD positive. Among the Rh antigens, the e antigen was positive in 97.8 % and 100% among the Rh(D) positive and Rh(D) negative donors respectively. No E antigen was detected in RhD negative donors. Total 6 and 2 Rh phenotypes were observed among the Rh(D) positive and negative donors respectively. R1R1 and Rr were the most frequent phenotypes among the RhD positive and negative donors (47.28% and 93.75%) respectively. Among the Kell blood group antigens, K and Kpb antigens were present in 100% of our donors while in Duffy and Kidd system Fya and Jka were most predominant (89% and 87%) respectively. Conclusions: The findings of the present study would be helpful in developing in-house panel cells. Moreover, a rare donor registry of donors typed negative for a high-frequency antigen can be formulated. IMC J Med Sci. 2024; 18(1):004. DOI: https://doi.org/10.55010/imcjms.18.004 *Correspondence: Soonam John, Department of Transfusion Medicine, Government Medical College, Parippally, Kollam, Kerala,India. Email: johnsoonam@gmail.com