Alcohol and other drug use are common in youth, but neurocognitive sequelae are unclear. This study examines the relationship between neuropsychological functioning and protracted substance use in adolescence. One hundred fifteen adolescents, ages 13 to 19 years, were recruited from inpatient substance abuse treatment programs and followed for 4 years. Adolescents were administered a comprehensive battery of neuropsychological tests and evaluated on substance use involvement during treatment, and at 6-month, 1-year, 2-year, and 4-year follow-up time points. Protracted substance abuse over the 4 years of follow-up was associated with significantly poorer subsequent functioning on tests of attention. In addition, alcohol and drug withdrawal accounted for significant variance in visuospatial functioning, above and beyond demographic, educational, and health variables in detoxified late adolescents and young adults. Results suggest that alcohol and drug withdrawal may be a more powerful marker of protracted neuropsychological impairments than other indices of youthful alcohol and drug involvement.