Evaluation of trends in the rate of infectious diseases of blood donors is essential for monitoring safety of blood supply and effective screening of donors. Transfusion records of blood donors who attended the Center between 2002 and 2005 were reviewed for positive cases of HBS (by ELISA), HIV (by Western Blot) and HCV (by ELISA). During 2002–05, 507,531 persons donated blood. The prevalence rates of HIV in 2002, 2003, 2004 and 2005 were 0.019%, 0.008%, 0.007% and 0.009%, respectively; the respective values were 0.57%, 0.52%, 0.53% and 0.53%, for HBS; and, 0.19%, 0.13%, 0.09%, and 0.16%, for HCV. The prevalence of HIV was higher in 2002 (p≤0.05). Then, it decreased, but remained constant over the following years. The prevalence rates of HBS, HCV and HIV were significantly (P<0.05) higher in the first-time, male and married blood donors. The values did not correlated with age of blood donors. The prevalence of transfusion-transmissible viral infections in Shiraz blood donors is less than normal population and did not change over time. This might be due to effective donor selection and the lower prevalence rate of these infections in donor population.