The main aim of this study was to determine how constructive thinking (CT), executive functioning (EF), and antisocial behavior (ASB) are related to drug use involvement in 282 adolescent females, 14-18 years of age, with a substance use disorder (SUD) and in controls. CT was measured using the Constructive Thinking Inventory (S. Epstein & P. Meier, 1989), EF was measured using a battery of neuropsychological tests, and ASB was measured using the Youth Self-Report Inventory (T. Achenbach, 1991) and a psychiatric interview. Females with an SUD demonstrated lower CT and EF scores and higher ASB scores compared with the controls. Low CT and low EF were significantly related to increased drug use involvement even when controlling for age, socioeconomic status, and vocabulary level. ASB partially mediated the relation between CT and drug use involvement, and it fully mediated the relation between EF and drug use involvement. Moreover, ASB moderated the relation between EF and drug use involvement.