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Objective: To determine the percentages of blood donors at an Ethiopian blood bank who tested positive for 4 transfusion-transmissible infections (TTIs) and to compare TTI infection levels among individuals of different sociodemographic characteristics.Method: We reviewed 5 years of data (2009 to 2013) from registration records of blood donors at the blood bank of Yirgalem Hospital in Hawassa, Ethiopia.Result: Of the 6367 donors, 447 (7.0%) tested positive for 1 of the TTIs for which infection necessitates discarding the infected blood unit. The prevalence of HIV (human immunodeficiency virus), HBV (hepatitis B virus), HCV (hepatitis C virus), and syphilis were 1.6%, 4.8%, 0.6%, and 0.5%, respectively. The prevalence of HIV was significantly increased among donors who were replacing blood for family members compared with volunteer donors (adjusted odds ratio [AOR], 0.34; 95% CI, .15 to .77), and employed donors compared with students (2.48; 1.22 to 5.02). HCV prevalence was significantly increased with replacement donors compared with volunteers. The prevalence of the 4 studied TTIs in volunteers' donations are lower than that in family replacement donation. The discard rate of blood from volunteers was 1.1%, versus 5.9% from replacement donors.Conclusion: The prevalence of TTIs is significant, and blood collected from volunteer donors is associated with lower risk of TTIs. Therefore, agencies must ensure a safe, adequate blood supply, designating unremunerated volunteers as a preferred donor group. Moreover, more sensitive and specific screening methods and a regular supply of materials and reagents must be provided to improve the quality standard of blood-bank laboratories.