Objective: Prescription opioid use disorder and overdose have emerged as significant public health challenges in the past 15 years. Little is known about public attitudes toward individuals who have developed a prescription opioid use disorder and whether these attitudes affect support for policy interventions. This study examined social stigma toward individuals with prescription opioid use disorder and tested whether stigma was associated with support for various policy interventions. Methods: A nationally representative Web-based survey was conducted from January 31 to February 28, 2014. The 1,071 respondents reported on their beliefs about and attitudes toward persons affected by prescription opioid use disorder and rated their support for various policy interventions. Ordered logistic regression models estimated the association between stigma and public support for punitive and public health-oriented policies. Results: Most respondents viewed this disorder as affecting all groups-racial and ethnic, income, and geographic area of residence groups-fairly equally, despite epidemiological data demonstrating that certain populations have been disproportionately burdened. Respondents expressed high levels of stigma toward individuals with prescription opioid use disorder. Levels of stigma were generally similar among those with and without experiencewith prescription opioid use disorder, either one's own or that of a relative or close friend. Higher levels of stigma were associated with greater support for punitive policies and lower support for public health-oriented policies. Conclusions: Reframing the issue to emphasize the structural factors contributing to prescription opioid use disorder and the barriers to accessing evidence-based treatment might improve support for policies that benefit affected individuals.