Background: Substance abuse is one of the main health challenges that lead to addiction and physical, psychological, and social issues. It can also eliminate the foundation of family and community. 
Objectives: The present study aimed at determining the frequency of experience of at least once abuse of addictive drugs in high school students in Hamedan, Iran.
Materials and Methods: The present cross-sectional study was carried out in 2015 in high schools of Hamedan City. A self-report questionnaire was used to identify the number of cigarette smokers and other addictive substances abusers. The data were analyzed, using SPSS V. 14.
Results: Out of 800 distributed questionnaires, 29 questionnaires were incomplete. In total, 18% of the students had abused addictive substances at least once. The most common substances were hookah, cigarette, and alcohol. Independent risk factors for substance abuse experience included male gender, non-governmental and vocational schools, mathematics major, history of the educational failure, an average of less than 17.00 GPA, unemployment of a student’s father, and student’s employment other than education.
Conclusion: The prevalence of hashish (cannabis) abuse and anabolic-androgenic steroids is high in Iran and codeine is the most commonly used substance in the non-prescribed groups.