Aim The aim of this study is to detect the prevalence of substance use among tenth-grade students; their thoughts, attitudes, behaviors, and tendencies towards substance use; and risk factors of substance use in tenth-grade students in general. Methods This study is descriptive and cross-sectional conducted between April and May 2016. Research population consists of tenth-grade students in 2015-2016 school year in the city of Ordu. Since the study involved all tenth-grade students, no sampling was done. Questions on substance use were prepared by Ordu Public Health Directorate and the authors by making use of European School Survey Project on Alcohol and Other Drugs (ESPAD) study questions, AMATEM's “Drugs and Addiction Youth Survey” study conducted on May 1996, and scientific studies conducted previously on similar subjects. Results 9825 tenth-grade students in 88 schools from 19 counties in the city of Ordu were included in the study. 8714 of the students participated in the survey. Being male, being over the age of 15, mother and father being separated, living with relatives, being in low income, negative feelings about school, perception of being unsuccessful in school, failing a year, absenteeism, and not being content with life are the risk factors for substance use. Conclusions The tendency of illegal substance use becoming more and more prevalent especially among youth requires the development of new treatment strategies.