National efforts have focused on improving adolescent substance use disorder (SUD) treatment outcomes, yet improvements remain modest. Because adolescents are noteworthy for heterogeneity in their clinical profiles, treatment might be enhanced by the identification of clinical subgroups for which interventions could be more effectively tailored. Some of these subgroups, such as those based on abstinence motivation, substance involvement, and psychiatric status are promising candidates. This study examined the unique predictive utility of adolescents' primary reason for alcohol and other drug use. Adolescent outpatients (N = 109; 27% female, aged 14-19) were assessed at treatment intake on their reason for substance use, as well as demographic, substance use, and clinical variables, and reassessed at 3, 6, and 12 months. Reason for use fell into two broad domains: using to enhance a positive state (positive reinforcement [PR]; 47% of youth) and using to cope with a negative state (negative reinforcement [NR]; 53% of youth). Compared with PR patients, NR patients were significantly more substance involved, reported more psychological distress, and had a more extensive treatment history. It is important to note that NR patients showed a significant treatment response, whereas PR patients showed no improvement. PR-NR status also uniquely predicted treatment response and outcome independent of a variety of other predictors, including abstinence motivation, self-efficacy, coping, and prior treatment. Adolescents' primary reason for substance use may provide unique clinical information that could inform treatment planning and patient-treatment matching.