OBJECTIVES: Given the rise in the population of arthritis and advances in the therapeutic options to manage arthritis, there are needs to evaluate the real-world pharmacotherapeutic management of arthritis. Therefore, we evaluated retrospective cross-sectional trends in prescription drugs utilization among adults with arthritis using a nationally representative data, the Medical Expenditures Panel Survey. METHODS: Study population comprised of bi-annual cross-sectional cohorts of individuals aged ≥ 18 years during calendar year of 2005 through 2014. Prescription drugs were classified based on therapeutic class and subclass as per Multum Lexicon database. Chi-square statistics were used to examine differences in the proportion of particular prescription drugs utilization between those with and without arthritis. RESULTS: An annual-weighted individual with doctor-diagnosed arthritis rose from 44.3 million in 2005/06 to 63.5 million in 2013/14. For arthritis-related medications, we found a gradual increase in single opioid agent use (4.7% vs. 13.3%), a minor increase in glucocorticoids (8.6% vs. 10.0%), as well as topical steroids (4.6% vs. 5.2%) and no changes in overall non-opioid analgesic use (46.3% vs. 45.0%) in 2013/14 as compared to 2005/06. With respect to co-medications, we found a stable use proportion of individuals utilizing cardiovascular agents (56.4%), central nervous system agents (57.0%), antibiotics (34.7%), and proton-pump Inhibitors (19.7%) from 2005/06 to 2013/14, whereas, an increase in proportion of individuals utilizing anticonvulsant (12.8% vs. 18.4%), statins (29.1 vs.35.0%), and antidepressant (22.8% vs. 24.9%) from 2005/06 to 2013/14 among those with arthritis. Individuals with arthritis were more likely to receive cardiovascular, central nervous system agents, gastrointestinal agents, respiratory agents as compared to those without arthritis throughout 2005/06 to 2013/14. CONCLUSIONS: Our study highlights an uptake of opioid analgesic with a relatively stable proportion of other arthritis-related medication. In addition, high use of cardiovascular, psychotherapeutic agents, antibiotics, gastrointestinal and respiratory agents suggest a significant medication burden among individuals with arthritis.