Introduction: Acquisition of transfusion transmissible infections in the process of therapeutic blood transfusion is a major global health challenge in transfusion medicine. This study aimed to determine the prevalence and trends of major transfusion transmissible infections among blood donors. Materials and Methods: A retrospective study, analysis of consecutive blood donors’ records covering the period between May 2018 and November 2019 was conducted to analyze for seroprevalence of HIV, HBV, HCV, VDRL and Malaria among blood donors and year trends were analyzed. Sterile venous anti-coagulated blood was collected from the donors and analyzed using highly sensitive and specific kits. Result: Out of the 5124 (4965 males and 159 females) individuals tested for HIV, HBV, HCV, VDRL and Malaria. Significantly declining trends of HIV, HBV, HCV, VDRL and Malaria (p<0.001) seroprevalence were observed over the two years study period. The seroprevalence of HIV was 0.13% in 2018 and showed no prevalence for next year afterwards. The seroprevalence of HBV decreased from 0.52 % in 2018 to 0.50% in 2019. No HCV prevalence in 2018 but 0.01% in 2019. Similarly, the prevalence of VDRL decreased progressively from 0.03% in 2018 to 0.01% in 2019. Conclusion: The low prevalence of HIV, HBV, HCV, VDRL and Malaria observed in present study may be due to awareness of donors, strict donor selection criteria and affective screening of the donors.