Background: Veterans are at higher risk of cancer than the general population due to older age, higher chronic tobacco use, alcohol use, environmental exposures, and other behavioral risk factors. Veterans who are diagnosed and treated for early stage cancer may expect long-term survival but face adverse effects of treatment including the risk of new persistent opioid use and related adverse outcomes including opioid use disorder. Veterans may be at higher risk for these outcomes given their high prevalence of mental health conditions including post-traumatic stress disorder (PTSD) and substance use disorder (SUD). Significance/Impact: The prevalence of cancer survivors in the Veteran population is increasing. It is essential that Veterans receive adequate pain management during cancer treatment but also that the long- term risks associated with chronic or unsafe prescription opioid use be minimized. The Centers for Disease Control (CDC) and the Veterans Health Administration/Department of Defense (VHA-DoD) have developed guidelines for safe use of prescription opioids but those guidelines exclude patients with cancer. It is essential to elucidate the pattern of and risks associated with prescription opioid use in this population and understand the risk factors associated with adverse outcomes. These findings can inform future guidelines and practice. Innovation: This study is innovate in seeking to describe the trajectory of opioid prescribing practices and the associated outcomes in a Veteran population treated for early stage cancer. Veterans have a distinct risk profile including a higher prevalence of mental health conditions including substance abuse that will inform the design of this study. The study is also innovative in examining these outcomes among Veterans dual enrolled in VA and Medicare Part D pharmacy benefits. Finally, the study is innovative in examining these outcomes across a range of cancer types that are common in the VA population. Specific Aims: The specific aims of this study are 1) to determine the incidence and patterns of new persistent opioid use, unsafe opioid prescribing practice, and associated adverse outcomes among Veterans in the 13 months following the treatment of early stage cancer, and 2) to identify factors associated with higher rates of new persistent opioid use and unsafe opioid prescribing patterns in this population. Methodology: This is a retrospective cohort study of Veterans who were diagnosed with cancer in the period 1/1/2015 to 12/31/2016. Eligibility criteria will include age 21 years and older, a new diagnosis of early stage cancer of the prostate, bladder, lung, oropharynx, colon, rectum, esophagus, stomach, liver, pancreas, or soft tissue (sarcoma), receipt of a definitive surgical procedure, and opioid naïve in the 12 months to 31 days prior to the index surgery. Outcomes will include new persistent opioid use, unsafe opioid prescribing practices, opioid use disorder, opioid overdose, and no...