BackgroundBlood transfusion services play a very key role in modern health care service delivery. About 118.5 million blood donations were collected globally in 2022. However, about 1.6 million units of blood are destroyed annually due to transfusion-transmissible infections (TTIs). There is a very high risk of TTIs through donated blood to recipients if safe transfusion practices are not observed. This study determined the prevalence and factors associated with TTIs among blood donors in Arua regional blood bank, Uganda.MethodsThis study was a retrospective cross-sectional design that involved a review of a random sample of 1370 blood donors registered between January 1st, 2018 and December 31st, 2019 at Arua regional blood bank, Uganda. Descriptive statistics were used to describe the characteristics of the blood donors. The binary logistic regression was used to determine the factors associated with TTIs.ResultsThe majority of the blood donors were male (80.1%), and the median donor age was 23 years (IQR = 8 years). The overall prevalence of TTIs was found to be 13.8% (95%CI: 12.0-15.6%), with specific prevalences of 1.9% for HIV, 4.1% for HBV, 6.6% for HCV and 2.8% for treponema pallidum. Male sex (AOR = 2.10, 95%CI: 1.32–3.36, p-value = 0.002) and lapsed donor type compared to new donor type (AOR = 0.34, 95%CI: 0.13–0.87, p-value = 0.025) were found to be associated with TTIs.ConclusionThe prevalence of TTIs among blood donors of West Nile region, Uganda was found to be significantly high, which implies a high burden of TTIs in the general population. Hence, there is need to implement a more stringent donor screening process to ensure selection of risk-free donors, with extra emphasis on male and new blood donors. Additionally, sensitization of blood donors on risky behaviors and self-deferral will reduce the risk of donating infected blood to the recipients.