Prescription-opioid misus e continues to be a significant health concern in the United States. The relationship between marijuana use and prescription-opioid misuse is not clear from the extant literature. This study examined national trends in prescription-opioid misuse among marijuana users and non-users using the 2007-2017 National Survey on Drug Use and Health. Cochran-Armitage tests were used to assess the statistical significance of changes in the yearly prevalence of prescription-opioid misuse and marijuana use. Multivariable logistic regression was used to examine the association between prescription-opioid and marijuana use adjusting for sociodemographic characteristics. From 2007 to 2017, marijuana use increased, while prescription-opioid misuse declined. Larger declines in prescription-opioid misuse were found among marijuana users than non-users. Marijuana ever-use was significantly associated with prescription-opioid misuse. Specifically, marijuana ever-users had higher odds of prescription-opioid misuse (ever-misuse [OR: 3.04; 95% CI, 2.68-3.43]; past-year misuse [OR: 3.44; 95% CI, 3.00-3.94]; and past-month misuse [OR: 4.50; 95% CI, 3.35-6.05]) compared to marijuana never-users. Similar results were found for the association of past-year and past-month marijuana use with prescription-opioid misuse. This study provides data on trends and associations about opioid misuse among marijuana users and non-users in a changing social environment of drug use in the United States. Future research should consider whether there is a causal relationship between marijuana use and prescription opioid misuse.