The peak risk of first extramedical use of prescription pain relievers (PPRs) is in mid-adolescence, often after underage drinking has begun. This research aims to investigate discrete classes of similar young people based on their newly incident extramedical use of PPR and alcohol involvement, with empirical evaluation of the underlying structure of identified subgroups and their epidemiological distributions in the United States. The U.S. National Surveys on Drug Use and Health, 2002-2013, sampled, recruited, and assessed 24,789 newly incident extramedical PPR users ages 12-20 years, with self-interviews on PPR, alcohol, and covariates. Latent classes of persistence were formed using PPR and alcohol status variables. Then, age and sex were studied as potentially important predictors of class membership. Analysis-weighted estimates and delta method variances were derived. Three classes were distinguished by extramedical PPR and alcohol use patterns: (a) nonpersistent (79%), (b) intermittent (15%), and (c) persistent (6%). There were no differences across classes by age, but being female was associated with greater odds of being in the intermittent class or persistent class compared to the nonpersistent class. Presenting clinical features of alcohol and/or opioid dependence that have become manifest at or near time of first PPR use can be indicators of persisting in extramedical use of PPR, particularly for young people who have recently started extramedical PPR use. Persistent adolescent and young adult extramedical PPR users require tailored public health prevention and intervention strategies based on their vulnerability to continue use over time. (PsycINFO Database Record (c) 2019 APA, all rights reserved).