BACKGROUND: In an effort to reduce barriers to screening for alcohol use in pediatric primary care, the National Institute on Alcoholism and Alcohol Abuse (NIAAA) developed a two-question Youth Alcohol Screening Tool derived from population-based survey data. It is unknown whether this screening tool, designed for use with general populations, accurately identifies risk among youth with chronic medical conditions (YCMC). This growing population, which comprises nearly one in four youth in the US, faces a unique constellation of drinking-related risks. METHOD: To validate the NIAAA Youth Alcohol Screening Tool in a population of YCMC, we performed a cross-sectional validation study with a sample of 388 youth ages 9-18 years presenting for routine subspecialty care at a large children's hospital for type 1 diabetes, persistent asthma, cystic fibrosis, inflammatory bowel disease, or juvenile idiopathic arthritis. Participants self-administered the NIAAA Youth Alcohol Screening Tool and the Diagnostic Interview Schedule for Children as a criterion standard measure of alcohol use disorders (AUD). Receiver operating curve analysis was used to determine cut points for identifying youth at moderate and highest risk for an AUD. RESULTS: Nearly one third of participants (n = 118; 30.4%) reported alcohol use in the past year; 86.4% (106) of past year drinkers did not endorse any AUD criteria, 6.8% (n = 8) of drinkers endorsed a single criterion, and 6.8% of drinkers met criteria for an AUD. Using the NIAAA tool, optimal cut points found to identify youth at moderate and highest risk for an AUD were ≥ 6 and ≥12 drinking days in the past year, respectively. CONCLUSIONS: The NIAAA Youth Alcohol Screening Tool is highly efficient for detecting alcohol use and discriminating disordered use among YCMC. This brief screen appears feasible for use in specialty care to ascertain alcohol-related risk that may impact adversely on health status and disease management.