Blood is a fluid which we have in our bodies that carries oxygen from the lungs to the rest of the body and also waste to be eliminated from the body. ABO and Rh blood group system is the most important system in transfusion and organ transplants. Though, many studies have been conducted in various parts of India to determine the local ABO and Rh distribution, no Indian study has so far been conducted to explore the South Indian especially Tamil Nadu and Pondicherry ABO and Rh distribution. The present study made an attempt to provide data on ABO and Rh blood group distribution across Tamil Nadu and Pondicherry. A total of 25,000 subjects of college students were included in this study and ABO and Rh(D) grouping was performed on all these samples. Data on the frequency of ABO and Rh(D) blood groups was expressed in simple numbers and percentages. The present study explored Among the ABO grouping system the highest frequency of blood group was found to be group O [10023(40.09%)], followed by group B [7447(29.79%)], and group A[ 6393(25.57%)]. The least common blood group was AB group [1137(4.55%)]. 94.69% Rh antigen was detected and the prevalence of Rh -ve was 5.13%. Of the 25000 individuals, the most common blood group was O followed by B and A and the least blood group was AB. The present study provides information about the relative distribution of various ABO blood grouping in the Tamil Nadu and Pondicherry. This vital information may be helpful in planning for future health care blood transfusion services.