Aims: Blood transfusion is a significant route of transmission of infection to recipients. The aim of the study was to analyse the prevalence of HIV, Hepatitis B, Hepatitis C, Syphilis and Malaria in voluntary and replacement blood donors, in a tertiary medical centre in Punjab. Methods: A total of 42275 blood donor units collected both in the blood bank and voluntary blood donation camps organized by the same, were tested over a two year period. Results: Of these, 23465 (55.5%) were voluntary donors and 18811 (44.5%) were replacement donors. The overall prevalence of transfusion transmitted infections (TTIs) was 4%. The prevalence of HCV was highest (2.3%) followed by Hepatitis B (0.7%), Syphilis (0.6%) and HIV (0.2%). Conclusion: Extensive screening of donor blood and promoting 100% voluntary donation can help improve blood safety.