<p><b>INTRODUCTION: </b>To determine the prevalence of prescription opioid (PO) use among Hispanics/Latinos with arthritis symptoms and to characterize how demographic and cultural factors are associated with PO use.</p><p><b>METHOD: </b>Cross-sectional analysis of baseline visit data during 2008 to 2011 from the Hispanic Community Health Study/Study of Latinos, a population-based cohort study of 16,415 Hispanics/Latinos living in Chicago, Illinois, Miami, Florida, Bronx, New York, and San Diego, California. Included participants self-reported painful inflammation or swelling in one or more joints. Multivariate models controlling for physical and mental health scores were constructed to assess how demographic and cultural factors were associated with PO use.</p><p><b>RESULTS: </b>A total of 9.3% were using POs at the time of the baseline visit. In multivariate models, persons of Cuban background (adjusted odds ratio [AOR] = 0.42, 95% confidence interval [CI; 0.21, 0.81]) and of Dominican background (AOR = 0.38, 95% CI [0.18, 0.80]) were significantly less likely to use POs compared with a reference group of persons of Mexican background. Greater language acculturation was also negatively associated with PO use (AOR = 0.68, 95% CI [0.53, 0.87]).</p><p><b>CONCLUSION: </b>POs were used relatively uncommonly, and use showed marked variation between Hispanic/Latino groups. Future study should determine mechanisms for why greater use of English among Hispanics/Latinos might influence PO use.</p>