Little is known about the adolescent risk factors and young adult health-related outcomes associated with running away from home. We examined these correlates of running away using longitudinal data from 4,329 youth (48% female, 85% white) who were followed from Grade 9 to age 21. Nearly 14% of the sample reported running away in the past year at Grade 10 and/or Grade 11. Controlling for demographics and general delinquency, running away from home was predicted by lack of parental support, school disengagement, greater depressive affect, and heavier substance use at Grade 9. In turn, runaways had higher drug dependence scores and more depressive symptoms at age 21 than non-runaways, even after taking these antecedent risk factors into account. Runaway status did not predict alcohol dependence risk at age 21. Results highlight the importance of substance use and depression, both as factors propelling adolescents to run away and as important long-term consequences of running away.