Objective: This longitudinal study had three aims: 1) determine the extent to which boys at high average risk and low average risk for substance use disorder differ on a construct of neurobehavioral disinhibition, 2) evaluate the capacity of neurobehavioral disinhibition to predict substance use frequency at age 16, and 3) demonstrate the utility of neurobehavioral disinhibition in predicting substance use disorder. Method: The authors derived an index of neurobehavioral disinhibition from measures of affect, behavior, and cognition. The neurobehavioral disinhibition score was used to discriminate youth at high and low average risk for substance use disorder and to predict substance use frequency after 4-6 years and substance use disorder after 7-9 years. Results: The neurobehavioral disorder score significantly discriminated boys at high average risk from those at low average risk at ages 10-12. Neurobehavioral disinhibition at age 16, in conjunction with substance use frequency and risk status group, predicted substance use disorder at age 19 with 85% accuracy and accounted for 50% of the variance in Drug Use Screening Inventory overall problem density score. Neurobehavioral disinhibition was a stronger predictor of substance use disorder (odds ratio=6.83) than substance consumption frequency (odds ratio=3.19). Conclusions: Cross-sectional and longitudinal analyses indicated that neurobehavioral disinhibition is a component of the liability to early age at onset of substance use disorder.