Overall, the results indicated that poor response inhibition predicted alcohol-related problems, the number of illicit drugs used, and comorbid alcohol and drug use. These results remained significant after controlling for IQ, parental alcoholism and antisocial personality disorder, child attention-deficit/hyperactivity disorder and conduct symptoms, and age. Other EF measures did not predict substance use onset after the other variables were considered. The findings suggest that EF problems may provide a target for behavioral interventions designed to break emerging patterns of substance abuse. Participants were 498 children living in families with high levels of alcohol use disorder (AUD) who were recruited from the community to take part in this multiwave study. Participants completed EF measures in early and late adolescence and reported on lifetime drinking and drug-taking at multiple points, including during late adolescence between the ages of 15 to 17 years. Parental alcoholism, child attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD), and child cognitive functioning were also assessed. Data analysis techniques included the calculation of zero-order correlations between the family and individual scores and the adolescence substance use outcome scores. Future studies should continue to probe the relationships between weak response inhibition and adolescent alcohol-related problems and illicit drug use. Tables, references