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Objective: The aim of this study was to evaluate the trends and gender differences in alcohol and substance use behaviors in youth admitted to an addiction treatment center in Istanbul. Methods: Participants were 2755 substance using children and adolescents who were treated at the Bakirkoy Mental Health and Neurologic Disorders Hospital between 2011 and 2014. The World Health Organization student drug use questionnaire was completed by trained clinicians. Results: There was an increase in the total number of youths admitted for substance use treatment (31.4% in 2011, 68.6% in 2014). A significant increase found in polysubstance use and in the number of females seeking treatment for substance use from 2011 to 2014. Alcohol, ecstasy, synthetics cannabinoids and heroin usage showed increase whereas inhalants, cannabis, prescribed medicines usage showed decrease in 2014. In 2014 while girls mostly consumed ecstasy, prescribed medicines and cocaine boys mostly used cannabis and synthetics. Conclusions: As new popular illicit drugs emerge in the market in the recent years, it is essential to reexamine the new trends in substance use and to reconsider prevention policies and treatment strategies. [Anadolu Psikiyatri Derg 2016; 17(4.000): 325-331]