Introduction: Little is known about the long-term outcome of substance misuse by teenagers, this is especially true for gender specific consequences. Objectives: To examine the prevalence of death, physical illnesses related to substance misuse, mental illness, substance misuse, criminality, and poverty in adulthood among two cohorts of individuals who as adolescents had consulted for substance misuse problems, to estimate the effect of sex on adverse outcomes, and to compare cohort effects. Methods: Individuals who had consulted a substance misuse clinic as adolescents during 1968-1971 and 1980-1984 were followed until 2002. Adverse outcomes were documented using information from Swedish national registers. Results: In the older cohort followed to age 50, only one-in-five escaped all six adverse outcomes, while over half of subjects experienced at least two or more. Sex and the severity of adolescent substance misuse and delinquency were predictors of adverse outcomes. More women than men experienced physical illness and poverty in the older cohort while more men than women were convicted of criminal offences in both cohorts and presented continued substance misuse in the younger cohort. Men in the younger as compared to the older cohort had higher rates of substance misuse and criminal convictions. Conclusions: Adolescents seeking help for substance misuse problems are at elevated risk for multiple adverse outcomes later in life. Outcomes differ for women and men and by severity of adolescent misuse and delinquency. Few cohort differences in adult outcomes exist.