Background: Blood-borne viral infections, like hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV), are most common during blood transfusion. Morbidity and mortality resulting from the transfusion of infected blood have far reaching consequences not only for the recipients themselves but also for their families, communities and the wider society. Aims: The study was designed to determine the prevalence of HBV, HCV and HIV among voluntary and replacement blood donors of Tripura, India, and to study the trends of HBV, HCV and HIV infections in the population. Materials and methods: This study is a retrospective cross-sectional study. The data was collected for consecutive 8 years from 2005 to 2013. Analyses were done in respect of total blood collection and HBV, HCV and HIV infections among the donors. Results: Among all donors, 91.8% was voluntary donors and 8.2% was replacement donors. The average HBV, HCV and HIV positivity was 1.2% (95% CI: 1.155-1.255), 0.109% (95% CI: 0.095- 0.125) and 0.093% (95% CI: 0.080-0.108) respectively. Among these, HBV seropositivity was 1.19% among voluntary donors and 1.33% among replacement donors and, in case of HCV and HIV, the seropositivity among voluntary and replacement donors were 0.109%, 0.11% and 0.089%, 0.145% respectively. HBV positivity was reduced in 8 years, whereas those of HCV and HIV remain unchanged. Conclusion: The most important observation of this study is gradual decrease in prevalence of HBV (p = 0.0018), whereas change in prevalence of HCV and HIV was not statistically significant. This might be due to mass hepatitis B vaccination program in Tripura.