Objective: Although neuropsychological evaluations are used as part of the basis for legal and rehabilitation decisions for juvenile delinquents, the effects of substance use on their neuropsychological functioning is not sufficiently addressed in the literature. The purpose of this study was to determine the influence of substance use on neuropsychological performance of juvenile delinquents. Method: Participants included 94 youth ages 12–17 with documented legal charges that resulted in court-mandated residential treatment or sentence to a corrections facility. Eleven regression analyses were conducted to determine the extent to which scores on the Drug Use Screening Inventory (DUSI) Substance Use scale predicted performance on measures of language, executive functions, visual-spatial ability, memory, and attention. Results: DUSI scores did not account for significant variance on ten neuropsychological measures. The Substance Use scale was a significant predictor of visual-spatial construction (B = −.25, t = −2.12, p < .05, CI = −.15 to −.01); however, the DUSI score accounted for only 5% of the variance in this measure. Conclusion(s): Overall, these findings indicate substance use as measured by the DUSI is not a significant influence on the neuropsychological functioning of juvenile delinquents. Significant findings on a test of visual-spatial construction are of uncertain significance and should be replicated. A limitation of this study is that the DUSI is a generalized drug and alcohol screening instrument. Future research should consider individual substances and use patterns, substance abuse trajectory, and associated use risk factors.