Adolescent substance use is linked with negative future outcomes (e.g., depression, anxiety, substance use disorder). Given that the brain undergoes significant maturation during adolescence, this developmental period may represent a time of particular vulnerability to substance use. Neuroimaging research has largely focused on heavy or binge patterns of substance use; thus, relatively less is known about the neural impact of a broader range of adolescent substance use. Characterizing the neural impact of a broader range of adolescent substance use may inform prevention and treatment efforts. The present study investigated relationships between adolescent substance use trajectories (i.e., alcohol, tobacco, and cannabis) and gray matter volume in young adulthood. Substance use was assessed in 1,594 participants at ages 11, 13, 16, and 19. Following the last assessment, 320 participants completed a single magnetic resonance imaging session to assess brain gray matter volume. Latent growth curve models were used to estimate growth parameters characterizing alcohol, tobacco, and cannabis use trajectories for each participant. These growth parameters (i.e., intercept, linear slope, and quadratic slope) were then used as predictors of gray matter volume. The gray matter volume of the hippocampus was positively associated with age 14 alcohol use (i.e., intercept) but not other trajectories (i.e., progression or acceleration) or substances (tobacco or cannabis). These results provide new insight into the neural impact of distinct adolescent alcohol, tobacco, and cannabis use trajectories, which may help to refine prevention and treatment efforts. (PsycInfo Database Record (c) 2024 APA, all rights reserved).