Background and Objectives: Providing safe blood and prevention of blood-borne infections are among the most important purposes of the Blood Transfusion Organization. The aim of this study was to describe the prevalence of Hepatitis B, C and HIV infection and their determinants in Zanjan blood donors from 2005 to 2006.Material and Methods: In this cross-sectional study, the prevalence of Hepatitis B, C and HIV infection was determined for a total sample of 29716 blood donors. Information on age, gender, educational level and marital status of the donors were collected. Eliza and confirmatory tests including RIBA and Western Blot were used to detect the positive samples for the infections. The data was analyzed using descriptive statistics and frequency tables.Results: From 29716 blood donors, 104 (0.3%) were positive for HBsAg, 33 (0.1%) for HCVAb and none for HIVAb. The prevalence of Hepatitis B increased with increasing age; it was greater in married than single and in illiterate than literate donors. Both B and C viral infections were more prevalent in the first time donors compared to the repeat donors.Conclusion: Although the prevalence of Hepatitis B, C and HIV infection was low in Zanjan blood donors, for providing a safe blood supply, educational programs and screening strategies among high risk groups such as those with lower levels of education, married and first time donors are recommended.