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Objective To examine longitudinal reciprocal relationships between marijuana use and psychiatric disorders, and identify the role of HIV in a sample (N = 340) of youth perinatally infected with HIV (PHIV+) and youth perinatally exposed but uninfected with HIV (PHIV−) (60.6% PHIV+; 9–16 years at baseline; 51% female). Methods Cross-lagged structural equation modeling was used to examine longitudinal associations between changes in marijuana use and changes in any behavioral, mood, and anxiety disorders at three time points across adolescence. Results Marijuana use predicted behavioral and mood disorders in youth, regardless of HIV status. Behavioral and mood disorders predicted marijuana use for PHIV− youth; behavioral disorders predicted marijuana use for PHIV+ youth. Anxiety disorders and marijuana use were not associated for either group. Conclusions For PHIV+ and PHIV− youth, interventions that target early marijuana use may reduce later psychiatric disorders. Similarly, treatment for early behavioral disorders may prevent subsequent marijuana use.