Objective: To assess the pattern of substance use disorder (SUD) in adolescents with and without history of attention-deficit/hyperactivity disorder (ADHD) using an Iranian sample in the context of a cultural background and drug availability is differing from Western countries. Method: In this case-control study, the participants were interviewed by a child psychiatrist and the measures included: kiddie Schedule for Affective Disorder and Schizophrenia for school age children (K-SADS), Opium Treatment Index (OTI) and Global Assessment Functioning (GAF). Data were analyzed with chi square test and T test and fisher exact test by EPI.6 software. Results: Adolescents with ADHD were younger at the time of starting cigarette smoking, substance use, abuse and dependency (p = 0.0001), a shorter period between their first-time substance use and substance dependence or abuse (p = 0.0001), more severe substance use (for cannabis, heroine, cigarette and drugs such as benzodiazepines p less than 0.05) and more functional impairment (p = 0.0007). Average number of co morbid disorders were higher in ADHD group. (p = 0.03) Conclusion: Although the pattern and type of substance use may be different in Iranian culture, our findings about the relationship between ADHD and SUD are similar to other western and non western countries. The presence of ADHD may over-ride cultural barriers and lower availability of drugs to the development of SUD in Iranian adolescents. Early diagnosis and treatment of ADHD may propose with better prognosis of SUD and subsequent decrease in the prevalence of SUD and the costs of SUD-related pathology in this population. (Contains 5 tables.)