Background: Blood safety is facing a major challenge in Egypt, having a high recorded prevalence of Hepatitis C virus antibodies (HCV Ab). Egypt is facing a new era after three years of starting the implementation of the new antivirals for HCV infected individuals and 25 years of the compulsory vaccination program of hepatitis B. Aim: to estimate the seroprevalence of Hepatitis B and C viruses, HIV, and Trepenoma Pallidum antibodies among blood donors in a university blood bank. Materials and Methods: A retrospective study was conducted at Suez Canal University blood bank based on official records. 53138 donors' data were analyzed from Jan 2015 to July 2018. Results: Among blood donors the prevalence of HCV Ab and HBsAg was 1.87 % and 0.97% respectively. No recorded positive cases of either HIV Ag-Ab or syphilis antibodies among the donated blood in this period. Percentages of positive HBsAg among family replacement donors (RD) and volunteer donors (VD) were decreased from 1.1% and 1.17 % in 2015 to 0.91% and 0.96% in 2018. Moreover, seropositivity for HCV Ab was declined in both RD and VD from 3% and 2.5% in 2015 to 1.3% and 1.4% in 2018, respectively. Conclusion: The prevalence of HCV and HBV is decreasing among blood donors and this may be attributed to the increasing awareness regarding blood-transmitted, hepatitis B vaccination, adherence to strict donation criteria, and introduction of oral direct acting antivirals.