Purpose To assess the prevalence and correlates of self‐reported misuse of prescribed‐opioid medications in the US general population. Method In 31 068 adult participants of the National Survey on Drug Use and Health (NSDUH) 2015 and 2016 who reported using opioids in the past year, we assessed the prevalence and correlates of self‐reported misuse of prescribed opioids, defined as using a larger dose, more frequently, or longer than prescribed. Multivariable logistic‐regression models and the machine‐learning method of boosted regression were used to identify the correlates of misuse. Results On the basis of weighted NSDUH estimates, of more than 89 million US adults who used prescription opioids every year, close to 3.9 million (4.4%) reported misused the prescribed medications. Prescribed‐opioid misuse was most strongly associated with co‐occurring misuse of opioids without a prescription, misuse of benzodiazepines, other drug‐use disorders, history of illegal activity, and psychological distress. Misuse of prescribed opioids was also strongly associated with prescription opioid–use disorder, especially among those who misused more potent opioids or started misusing opioids before the current year. Conclusions Misuse of prescribed opioids is associated with other high‐risk behaviors and adverse health outcomes. The findings call for better monitoring of opioid prescription in clinical practice.