Knowledge, attitudes and practices (KAPs) regarding HIV/AIDS is one of the corner stone inrnthe fight against the disease. Youths, especially high school students, are most vulnerable torninfection, among others due to lack of adequate information, bad attitude towardsrnPLWHIV/AIDS, and risky sexual practices. Evaluation of their KAPs remains crucial inrndesigning appropriate prevention strategies. This study sought to investigate the determinantsrnof HIV/AIDS transmission and prevention knowledge, attitude and practice among highrnschool students in Yeka Sub City of Addis Ababa. The study employed multivariate binaryrnlogistic regression to analyze the patterns and determinants of the disease, using crosssectional data collected from randomly selected 608 students aged 15â€“22 years. Allrnrespondents reported to have heard about HIV/AIDS before. However, misconceptions aboutrnroutes of transmission were observed in 20 % of respondents. In addition, out of the totalrnstudy participants, 89 (14.6%) have ever been exposed to sexual intercourse, but only 20rn(22.47%) of them used condom during intercourse. In terms of determinants, students, whornwere at higher grade level, were more likely to have higher HIV/AIDS transmission andrnprevention knowledge than those in lower grade levels (AOR: 15.5; P=0.001: 95 % CI:rn3.036- 80.05). Respondents whose mothers achieved secondary education compared to thosernstudents whose mothers were unable to read and write were more likely to have more positivernattitude towards PLWHIV/AIDS (AOR: 0.24; P=0.007; 95% CI: 0.06-66). Students had arnsatisfactory level of knowledge on HIV/AIDS transmission and prevention. None-the-lessrnmisconceptions about HIV transmission, intolerance and discriminatory attitudes towardsrnPLWHIV, and risky sexual practices were observed among study participants, which can bernminimized by boosting their knowledge through sex education since the latter was their mainrnsource of information on HIV/AIDS. In addition, maternal education status and fathersâ€™rneducation status are also determinants of high school student HIV/AIDS KAP so there shouldrnreinforcement of educational interventions particularly in the secondary school and Parentsrnshould be thought, and work with to change their attitude and belief about communicationrnwith their children in order to protect youth from the virus.