Current cognitive-motivational addiction theories propose that prioritizing appetitive, reward-related information (attentional bias) plays a vital role in substance abuse behavior. Previous cross-sectional research has shown that adolescent substance use is related to reward-related attentional biases. The present study was designed to extend these findings by testing whether these reward biases have predictive value for adolescent substance use at three-year follow-up. Participants (N = 657, mean age = 16.2 yrs at baseline) were a sub-sample of Tracking Adolescents' Individual Lives Survey (TRAILS), a large longitudinal community cohort study. We used a spatial orienting task as a behavioral index of appetitive-related attentional processes at baseline and a substance use questionnaire at both baseline and three years follow-up. Bivariate correlational analyses showed that enhanced attentional engagement with cues that predicted potential reward and nonpunishment was positively associated with substance use (alcohol, tobacco, and cannabis) three years later. However, reward bias was not predictive of changes in substance use. A post-hoc analysis in a selection of adolescents who started using illicit drugs (other than cannabis) in the follow-up period demonstrated that stronger baseline attentional engagement toward cues of nonpunishment was related to a higher level of illicit drug use three years later. The finding that reward bias was not predictive for the increase in substance use in adolescents who already started using substances at baseline, but did show prognostic value in adolescents who initiated drug use in between baseline and follow-up suggests that appetitive bias might be especially important in the initiation stages of adolescent substance use.