BackgroundPrior research on prescription drug misuse has focused on identifying individual risk factors. While a few studies examine differences in misuse based on geographic residence, there is a lack of research that examines the relevance of neighbourhood characteristics. MethodsThe current research used data from the 2000 National Household Survey on Drug Abuse, a sample of respondents that was generalizable to the non-institutionalised population of the United States. Logistic regression models were estimated to examine the relationship between neighbourhood characteristics (e.g., social disorganisation, social capital, and social participation) and prescription drug misuse (e.g., any misuse, pain reliever misuse, sedative/tranquiliser misuse, and stimulant misuse) among adolescent respondents ages 12–17. ResultsFindings show that neighbourhood characteristics were significantly associated with any prescription drug misuse and also the misuse of prescription opioids. Adolescents in socially disorganised neighbourhoods and also those in neighbourhoods with lower levels of social capital were more likely to report prescription drug misuse. Interestingly, adolescents with greater levels of social participation were more likely to report prescription drug misuse. ConclusionThese findings were largely consistent with prior research examining the significance of neighbourhood characteristics in relation to crime and deviance. In order to adequately address the ongoing prescription drug epidemic in the United States, policy makers must address the neighbourhood characteristics that are known to be associated with prescription drug misuse.