Background : poor oral health can affect a person’s day today as well as overall quality of life. Discomforts from experience of pain, problems with eating and chewing, embarrassment about the shape, missing, discolored or damaged teeth can adversely affect peoples’ daily lives and well-being. The aim of this study was to assess the knowledge, attitude and practice of oral hygiene among preparatory students of Medhanealem high School in Addis Ababa, Ethiopia. Method : A cross sectional study design was conducted using a self-administered questionnaire from June to September 2019 in Medhanealem high school, Addis Ababa. Data was analyzed using SPSS V.20 and a descriptive statistics was employed to present results on knowledge, attitude and practices of high school students towards oral hygiene. Result : A total of 320 students have participated in the study, of whom 207(64.7 % ) were female. The study revealed that 201(62.8 % ) of the respondents had poor knowledge with regard to oral hygiene, about half (52.1 % ) of the students had negative attitude toward oral hygiene, and their oral hygiene practices were still low that 193 (60.4 % ) of the students reported inadequate practice. The chewed stick (mefakiya) is the most common oral hygiene aid used for cleaning teeth which was adopted by 134(51 % ) students. Conclusions : The study showed that oral hygiene knowledge, attitude and practice among the secondary school students in Medanealem preparatory school were not satisfactory. The findings of this study suggest that awareness on the importance of oral hygiene needs to be enhanced along with regular education.