We aimed to estimate utilization rates of prescription opioids among adults with chronic pain in the United States (US) and identify factors associated with the frequent or daily use of prescription opioids. This was a case-control analysis of the 2019 National Health Interview Survey of adults. Over 50.2 million adults in the US reported chronic pain in the past 3 months, but only 10.5% of this group said they used prescription opioids frequently or daily to manage their pain. Adults with chronic pain were significantly more likely to use opioids if they had incomes below the federal poverty level (15.7%), relied on public health insurance (14.8%), had been hospitalized in the past year (17.8%), or rated their health as fair or poor (18.4%). The highest rates of opioid use were reported among adults with severe (24.4%) or moderate disability (18.9%). Approximately 5.3 million adults use prescription opioids frequently or daily to manage chronic pain. These individuals should receive regular clinical assistance to manage their pain, including medication management and, when appropriate, referral to evidence-based treatment programs for opioid use disorder.