OBJECTIVE To examine the relationship of adolescent alcohol and drug use over a 5-year period to cumulative health problems in late adolescence and young adulthood. METHODS We prospectively examined self-reported health problems in a sample of adolescents, some of whom received treatment for substance use disorders and had consistently poor substance use outcomes (n = 38), some of whom received treatment for substance use disorders and had positive substance use outcomes (n = 30), and a low alcohol and drug use community comparison group (n = 48). Data regarding health-related problems of these adolescents (mean, 15.9 years; 83% Caucasian; 56.5% female) were collected at 2, 4, and 6 years following initial assessments. RESULTS Alcohol and/or drug involvement severe enough to warrant treatment during adolescence was associated with more cumulative health problems and severe health problems for girls and more cumulative health problems for boys. Protracted and continuous abuse of alcohol and drugs was associated with more cumulative and severe health problems for girls and more severe health problems for boys. CONCLUSIONS These results suggest that significant health problems and concerns are related to both brief and protracted alcohol and drug abuse during adolescence. Health problems will likely become even more evident as early-onset, chronic substance abusers continue to age.