INTRODUCTION: Premarital sexual practice is sexual intercourse experienced before marriage. It usually leads to sexual and reproductive health problems that are the main causes of death, disability and disease among young people in the world particularly in Africa including Ethiopia. OBJECTIVE: To assess the magnitude of premarital sexual practice and associated factors among Adigrat high school students, Ethiopia, 2015. OBJECTIVE: To assess the magnitude of premarital sexual practice and associated factors among Adigrat high school students, Ethiopia, 2015. METHODS: A school based cross-sectional study was conducted through self-administered questionnaires. The sample size was determined using single population proportion formula. Data was entered and cleaned using EPI info version 7 and exported and analyzed using Statistical Package for Social Sciences (SPSS) version 20. Logistic regression model was used to measure the association of outcome and independent variables. RESULT: 567 Adigrat high school students participated in the study. This study revealed that 17.6% of the study participants had practiced premarital sexual intercourse before the study period. The variables found to be associated with premarital sexual practice were, educational level, attending entertainment programs, sexual communication with friends and use of addictive substances. CONCLUSION AND RECOMMENDATION: There were a substantial proportion of high school students who practiced premarital sexual intercourse. Therefore, collaborative effort needs to address sexual and reproductive health issues of students related to premarital sexual practice.