Genetic, physiological and psychological investigations have demonstrated that deficient inhibitory regulation amplifies the risk for substance use disorder (SUD). This study extends this line of research by determining the association between childhood neurobehavior disinhibition and decision to desist substance use following prevention intervention during adolescence. The sample consisted of 302 boys who were evaluated at ages 10-12, 12-14, 16, and 19. Results indicated that childhood neurobehavior disinhibition negatively covaried with decision to desist substance use during adolescence. These two variables predicted acceleration of drug consumption frequency during adolescence and DSM-IV diagnosis of SUD by age 19. Decision to desist drug use did not mediate the association between neurobehavior disinhibition and substance use/SUD. The findings indicate that substance abuse prevention would be potentiated by ameliorating childhood neurobehavior disinhibition.