Background: A total of thirty five (35) blood group systems has been discovered till date. It has been illustrated in the various transfusion literatures that particular disease is associated with particular type of blood group systems. The present study was conducted with the aim to determine the pattern of distribution and to detect any association of transfusion transmitted infections (TTI) with ABO and Rh blood groups. Materials and Methods: A retrospective study was done at the blood bank Shaheed Hasan Khan Mewati (SHKM) Government Medical College Nalhar Haryana, India over a period of 6 year 5 month (August 2013 to December 2019) . A total of 28,812 healthy donors were included in the study. All the donor blood unit were screened for HbsAg, HIV, HCV, Syphilis and Malaria. Results: The most common blood group was B (39.91%). The total seroreactivity of TTI was 3.8% ( 1096 out of 28,812). Out of the total, 2.88% (831 out of 28,812) cases were reactive for HBsAg, 0.29% (86 out of 28,812) for HIV, 0.565% ( 163 out of 28,812) for anti HCV, 0.0138% (4 out of 28,812) for syphilis and 0.0416% (12 out of 28,812) for Malaria. Maximum seroreactivity was seen in blood group B (5.0%) followed by A (3.6%) and O group (3.1 %) and then AB (1.1%). A significant association was seen between Rh positive blood group and HBsAg seropositivity (P value of 0.0459). There was significant association between syphilis infection and AB blood group with a p value of 0.0331 among syphilis positive donors. Conclusion: This study provides the prevalence of ABO and Rh blood group and also their association with the transfusion transmitted infections (TTI). This study shows a significant association between Rh positive blood group and HBsAg and also significant association was seen between AB blood group and syphilis infection.