Abstract Providers who treat adolescents with co-occurring substance use and mental health issues may prioritize treatment of one set of symptoms believing that improvements in one domain will result in improvements of the other. However, limited empirical data for adolescents provide evidence of such “spillover effects.” Using data from 2900 youth in an outpatient treatment, we examined whether during-treatment changes in substance use or mental health symptoms predicted 12-month outcomes in the analogous and opposite domains. There was very little evidence of spillover effects, only that youth with no internal distress at 0 and 3 months reported lower levels of substance use problems at 12-months relative to youth with internal distress that stayed the same from 0 to 3 months. These findings suggest that providers treat both sets of substance use and mental health symptoms in an integrated manner given that these symptoms commonly co-occur among youth with either set.