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Nonmedical use of prescription opioids (NUPO) is associated with heroin use and other adverse outcomes among adolescents. To inform the timing of substance use prevention activities and which substances to target, we examined age at NUPO initiation, associations between substance use initiation and current (past 30-day) NUPO, and order of NUPO initiation relative to other substances. Data from 2,834 students aged 15 or older participating in the 2017 Virginia Youth Survey, the first Youth Risk Behavior Surveillance System survey to asse