Background: Human blood groups are genetically inherited and exhibit varying degrees of polymorphism. There is significant difference in the frequency of distribution of the various blood groups in population. Of the various blood group systems, the ABO and Rh blood group system is the most important blood group system in health and disease. Aim: To find out the correlation between the transfusion transmitted infections (TTIs) like Human Immunodeficiency Virus (HIV–1and HIV–2), Hepatitis–B Virus (HBV), Hepatitis–C Virus (HCV), Syphilis and Malaria and ABO and Rh blood groups among the apparently healthy human blood donors. Material and Methods:This was a retrospective record based study conducted at Department of Immunohematology and Blood Transfusion (I.H.B.T.) of Government Medical College and S.S.G. Hospital, Baroda, Gujarat from January 2016 to April 2019. A total of 45,549 donors were included in the study. All the blood units were screened for HIV, HBV, HCV, Syphilis, and Malaria. Results and conclusion: Seropositivity for TTIs was found to be more in Rh positive donors. Blood group A positive showed highest seropositivity for TTIs (1.79%) and blood group AB negative showed least seropositivity for TTIs (0.56%).