BackgroundAlthough the demand for blood supply has progressively increased in developing countries, evidences indicate that there is a major shortage of blood and blood products in these countries, particularly in Ethiopia. Thus, identifying motivational factors affecting blood donation and recruitment of safe and low risk donors is necessary. For this reason, the study aimed at assessing knowledge, attitude, and practice towards blood donation and its associated factors.MethodsA community based cross-sectional study was conducted in Debre Markos town from February to April, 2015. Multi-stage sampling technique was employed to recruit a total of 845 study participants. Interviewer administered questionnaire was employed as a data collection tool. Binary logistic regression was applied to assess the relationship between explanatory variables and outcome variables.ResultsIn this study, 436 (56.5 %) and 403 (52.2 %) were found to be knowledgeable and having favorable attitude, respectively, while the other 124 (16.1 %) reported to have the practice of blood donation. Younger age group, male sex, those who attended formal education and radio listener were significantly associated with the knowledge of blood donation. Attending secondary and above education, having higher income, listening to radio broadcasts, and knowledge of blood donation were found to be the independent predictors of attitude. The practice of blood donation was higher among respondents who were older, attended certificate and above education, knowledgeable, and favorable attitude groups.ConclusionThe prevalence of knowledge and practice of blood donation is found to be higher compared to similar study conducted in Mekelle, whereas the level of attitude is found to be lower. The finding of this study also justified any possible interventions on the independent predictors. There should be a regularly scheduled awareness creation and voluntary blood donation campaigns organized at the community level to utilize potential blood donors.