The relationship of diagnosis, developmentally relevant factors (e.g., life stress, peer substance use) and mental health symptoms to contexts of a return to substance use were examined for 103 substance abusing adolescents with Axis I psychopathology (ages 12-17) following inpatient treatment. Proximal psychiatric symptoms and developmentally relevant factors, but not psychiatric diagnosis at treatment entry, predicted contexts in which youth returned to alcohol and drug use in the 6 months following treatment. The findings suggest that comorbid youth are similar to same-aged peers without comorbid psychopathology and adults with comorbid psychopathology in regard to contexts associated with a return to substance involvement.