Blood transfusion is an important mode of transmission of infections to recipients. Evaluating trends in the prevalence of transfusion transmissible infections among blood donors is essential for monitoring blood supply safety and donor screening effectiveness. This study aimed to assess the seroprevalence of transfusion-transmissible infections among blood donors in the blood bank of a tertiary care teaching hospital in Bangalore, India. All consenting blood donors were consecutively included from Jan 2012 to Dec 2015 and were screened for seroprevalence of HIV, HBV, HCV and syphilis. A total of 4087 donors were tested, out of which 2681(65.6%) were replacement donors, 1406 (34.5%) were voluntary donors and 93% were males, 6.5% were females. The overall seropositivity rates of HIV, HBV, HCV & Syphilis were respectively 0.2%, 0.75%, 0.34% & 0.3% respectively. None of them were positive for malarial parasite. Seropositivity was more among males than in females and in replacement donors when compared to voluntary donors. Thus there is the need for non-remunerated voluntary donor services to be instituted. Also further prevalence rates of HCV and Syphilis to be studied in this region as there is greater fluctuation among them so that necessary steps are taken to provide safe blood to the recipients.