The prescription opioid epidemic, beginning in the late 1990’s saw massive expansion of opioid prescriptions nationwide, ultimately leading professional societies, healthcare systems, and legislative bodies to take measures curbing inappropriate prescription of opioids, particularly at high doses and for chronic use. While some of these have had dramatic and sustained overall effects, there is little known about how trends in opioid prescription, nor opioid-related adverse events and mortality have changed for the cancer survivor population. Moderate to severe cancer pain warranting opioid therapy is very common, and as the cancer survivor population continues to grow, so too does the need to understand how opioid-related policies (even those specifically excluding people with cancer) has affected access to appropriate pain management. This project uses a matched longitudinal cohort methodology in two distinct populations (US veterans and Medicare beneficiaries) in order to longitudinally and quantitatively characterize in people with cancer changes in: opioid prescription rate and dosage, duration of opioid therapy, choices of opioids, opioid-related hospitalizations and emergency department visits, new diagnosis of opioid abuse or dependence, as well as ER visits or hospital admissions for opioid-related adverse events, enrollment in Medication-Assisted Treatment (MAT) programs, and the case fatality rate of opioid overdose events. By studying these events between 2008-2018, we will be able to evaluate the effects of several waves of opioid-related guidelines, policies, and laws at the healthcare system, state, and federal level to see how cancer patients have been affected by the US response to the prescription opioid epidemic. Finally, a second aim of the study will be to use a nested case-control study to specifically analyze opioid overdose events in people with cancer versus those who do not, in order to characterize risk factors for fatal overdoses, including access to prescription opioids. Ultimately, this project has the potential to close several key gaps in the understanding of the prescription opioid epidemic in people with cancer, which could in the immediate term help patients and clinician to better evaluate the risks and benefits of opioid therapy, and in the longer term allow policymakers and professional societies to have a more precise understanding of spillover effects of opioid-related policies on people with cancer.