Background. When 12-to-21-year-olds start using prescription pain relievers extra-medically, some of them transition into opioid dependence within 12 months after such use. Our main aim for this epidemiological research on 12-to-21-year-olds in the United States (US) is to estimate the risk of becoming a newly incident case of opioid dependence within 12 months after onset of using prescription pain relievers extra-medically (EMPPR).Methods. Meta-analyses from multiple independent replication samples now are possible, based upon nationally representative survey samples of US adolescents age 12–21 years. All 12-to-21-year-olds were sampled and recruited for the US National Surveys on Drug Use and Health, with standardized assessments of EMPPR use and opioid dependence (NSDUH, 2002–2013).Results. Peak risk for a transition from start of EMPPR use to opioid dependence within 12 months is seen at mid-adolescence among 14-to-15-year-olds (6.3%, 8.7% per year), somewhat earlier than peak risk for starting EMPPR use (seen for 16-to-19-year-olds at 4.1%, 5.9% per year). Applied to 12-to-21-year-olds in the US between 2002–2013, an estimated 8 million started using PPR extra-medically. Each year, roughly 42,000 to 58,000 transitioned into opioid dependence within 12 months after onset of such use.Discussion. These epidemiological estimates for the US in recent years teach us to expect one transition into adolescent-onset opioid dependence within 12 months for every 11–16 newly incident EMPPR users, yielding perhaps 120 newly incident opioid dependent cases in need of practitioner attention or treatment services, each day of each year. This evidence can be used to motivate more effective public health prevention, outreach, and early intervention programs as might prevent or delay occurrence of EMPPR use and opioid dependence.