BACKGROUND: The National Institute on Alcohol Abuse and Alcoholism (NIAAA) 2-question screen is a valid adolescent alcohol screening tool. No studies have examined if this tool predicts future alcohol problems. We conducted a study at 16 pediatric emergency departments to determine the tool's predictive validity for alcohol misuse and alcohol use disorders (AUDs). METHODS: Participants (N = 4834) completed a baseline assessment battery. A subsample of participants completed the battery at 1, 2, and 3 years follow up. RESULTS: Of the 2209 participants assigned to follow-up, 1611 (73%) completed a 1-year follow-up, 1591 (72%) completed a 2-year follow-up, and 1377 (62%) completed a 3-year follow-up. The differences in AUDs between baseline NIAAA screen nondrinkers and lower-risk drinkers were statistically significant at 1 year (P = .0002), 2 years (P <.0001), and 3 years (P = .0005), as were the differences between moderate- and highest-risk drinkers at 1 and 2 years (P < .0001 and P = .0088, respectively) but not at 3 years (P = .0758). The best combined score for sensitivity (86.2% at 1 year, 75.6% at 2 years, and 60.0% at 3 years) and specificity (78.1% at 1 year, 79.2% at 2 years, and 80.0% at 3 years) was achieved by using "lower risk" and higher as a cutoff for the prediction of a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis. CONCLUSIONS: The NIAAA 2-question screen can accurately characterize adolescent risk for future AUDs. Future studies are needed to determine optimaluse of the screen.