Background: Non-medical use of prescription opioids carries risks including development of abuse/dependence. Such use may correlate with psychiatric, medical. and substance use characteristics. Methods: Cross-sectional survey, the 2002-2004 National Survey on Drug Use and Health. Respondents 18 years and older (n = 91,823). Bivariate and multivariable associations were investigated. Results: The prevalence of past-year non-medical use of prescription opioids was 4.5%. Of those with non-medical use, 12.9% met criteria for abuse/dependence. On multivariable analysis, past-year non-medical used was associated with panic (AOR 1.2; 95% CI 1.04-1.5), depressive (AOR 1.2; 95% CI 1.01-1.5) and social phobic/agoraphobic symptoms (AOR 1.2; 95% CI 1.1-1.4). Among those with past-year non-medical prescription opioid use, those with abuse/dependence were more likely to have panic (AOR 1.7; 95% CI 1.2-2.4) and social phobic/agoraphobic symptoms (AOR 1.7: 95% Cl 1.2-2.4). In addition, they were more likely to report fair/poor health (AOR 2.1; 95% Cl 1.4-3.0), have misused another class of prescription medication (AOR 1.7; 95% Cl 1.2-2.3), have used heroin (AOR 2.9; 95% CI 1.2-6.9) and initiated substance use before the age of 13 (AOR 4.7 : 95% CI 1.1-19.9). Conclusions: Non-medical use of prescription opioids is common. Furthermore, nearly 13% of those with non-medical use meet criteria for abuse/dependence. Panic, social phobia and agoraphobia, low self-rated health status, and other substance misuse among those with non-medical use of prescription opioids should alert clinicians to screen for abuse and dependence. (c) 2007 Elsevier Ireland Ltd. All rights reserved.