<i>Background: </i>Blood transfusion is an effective treatment for saving millions of lives, even though transfusion-transmissible infections are the major problem. The prevalence of transfusion-transmissible infections varies between different geographical populations. This study aims to assess the prevalence of transfusion-transmissible infections and associated factors among blood donors at Woliso Blood Bank, South West Shewa Zone, Oromia, Ethiopia. <i>Method: </i>An institutional-based cross-sectional study design was conducted. A structured and pre-tested questionnaire was used to collect data through a face-to-face interview. The data was entered in Epi Data version 3.1, and exported to STATA version 17.0 for data cleaning and analysis. A binary logistic regression analysis was performed to identify factors associated with outcome variables. Odd ratios along with the 95% confidence interval were used to present the finding and statistical significance was reported with a p-value of 0.05. <i>Results: </i>The overall prevalence of transfusion-transmissible infections was 9.5% (95% CI 6.3-12.9%). Participants without formal education [AOR=4.84; 95% CI= 1.09, 21.46], unprotected sexual intercourse with multiple partners [AOR=4.77; 95% CI= 1.38, 16.44], and participants with a lower frequency of blood donation [AOR=2.85; 95% CI: 1.16, 6.99] were significantly associated with transfusion transmissible infections. <i>Conclusions: </i>The prevalence of transfusion-transmissible infections was high in this study area. Educational level, unprotected sexual intercourse with more partners, and a number of blood donations were found to be independent predictors of transfusion-transmitted infections. Blood banks and regional health offices should work to mobilize the community and improve health promotion through prevention and control considering the associated factors identified.