ABSTRACT: To determine longitudinal associations between patterns of comorbid cigarette, alcohol, and marijuana use and Antisocial Personality Disorder (ASPD), Major Depressive Episode (MDE), and Generalized Anxiety Disorder (GAD) in adulthood.A random community-based sample [X? age=36.6 (SD=2.8)] from the Children and Adults in the Community Study, an on-going investigation of substance use and psychiatric disorders. Data were collected at six time waves. Conjoint trajectories of cigarette, alcohol, and marijuana use spanning adolescence to adulthood were determined; multivariable logistic regression analyses assessed associations between trajectory group membership and having ASPD, MDE, or GAD in adulthood.Five conjoint trajectory groups were obtained: HHH (chronic cigarette, alcohol, and marijuana use), DDD (delayed/late-starting cigarette, alcohol, and marijuana use), LML (low/no smoking, moderate alcohol use, occasional marijuana use), HMN (chronic smoking, moderate alcohol use, no marijuana use), and NON (occasional alcohol use only). Compared with members of the NON group, those in the HHH group had significantly greater odds for having ASPD (Adjusted Odds Ratio [AOR]=28.52, 95% Confidence Interval [CI]=9.44-86.17), MDE (AOR=2.67, 95% CI=1.14-6.26), and GAD (AOR=6.39, 95% CI=2.62-15.56). Members of the DDD, LML, and HMN groups had weaker and less consistent associations with the three psychiatric outcomes.In a large, community-based sample, long-term concurrent use of more than one substance was associated with both externalizing and internalizing psychiatric disorders in adulthood. Prevention and treatment programs might target individuals in the community and general clinical populations with comorbid substance use, even if they haven't been identified as having a substance use disorder.