Introduction
In Ethiopia, more adolescents are in school today than ever before; however, there are no studies that have assessed their comprehensive knowledge of HIV/AIDS. Thus, this study tried to assess the level of this knowledge and the factors associated with it among in-school adolescents in eastern Ethiopia.

Methods
A cross-sectional school-based study was conducted using a facilitator-guided self-administered questionnaire. The respondents were students attending regular school in 14 high schools located in 14 different districts in eastern Ethiopia. The proportion of in-school adolescents with comprehensive HIV/AIDS knowledge was computed and compared by sex. The factors that were associated with the comprehensive HIV/AIDS knowledge were assessed using bivariate and multivariable logistic regression.