Background: The opioid epidemic is a complex national crisis in the United States with a 400% increase in related deaths over the past two decades with no signs of slowing. The purpose of this study was to assess the incidence of opioid use, based on the geographic and population characteristics. Methods: The opioid-related hospital inpatient stays and emergency department visits obtained from the 2010 to 2018 Healthcare Cost and Utilization Project and demographic confounders, including age, race, education, and income gathered from US Census data were analyzed through generalized linear mixed models and reported by community size and region. Results: Opioid use varies among population center sizes and the region analyzed. In general, opioid visits in the southwest region were greatest across the majority of population center sizes. Rural usage was greatest in the northeast, southeast, and southwest. Unemployment and diverse ethnicities were commonly associated with opioid use in the metro areas studied but these associations were not seen in rural areas. Conclusion: Opioid use remains significant among diverse populations across the United States. Understanding the unique dynamics associated with opioid usage in populations within the regions studied is important in guiding future interventions to fight this crisis.