Cannabis use and depression are two of the most prevalent conditions worldwide. Adolescent cannabis use is linked to depression in many studies, but the effects of adolescent cannabis involvement on young adult depression remain unclear and may differ for males versus females. In this cohort study of youth from a mid-Atlantic metropolitan area of the United States, repeated assessments from 1985 (at age 6 years) through 2002 (at age 21 years) were made for 1,494 individuals (55% female). Measured covariate differences between individuals with and without cannabis problems were controlled via propensity score techniques. The estimated risk of young adult depression for adolescents with cannabis problems was not significantly different from that for comparison adolescents for either females (odds ratio = 0.7, 95% confidence interval: 0.2, 2.3) or males (odds ratio = 1.7, 95% confidence interval: 0.8, 3.6). The evidence does not support a causal association linking adolescent-onset cannabis problems with young adult depression.