US military Veterans have been disproportionately impacted by the US opioid overdose crisis. In the fall of 2019, the Veterans Health Administration (VHA) convened a state-of-the-art (SOTA) conference to develop research priorities for advancing the science and clinical practice of opioid safety, including both use of opioid analgesics and managing opioid use disorder. We present the methods and consensus recommendations from the SOTA. A core group of researchers and VA clinical stakeholders defined three areas of focus for the SOTA: managing opioid use disorder, long-term opioid therapy for pain including consideration for opioid tapering, and treatment of co-occurring pain and substance use disorders. The SOTA participants divided into three workgroups and identified key questions and seminal studies related to those three areas of focus. The strongest recommendations included testing implementation strategies in the VHA for expanding access to medication treatment for opioid use disorder, testing collaborative tapering programs for patients prescribed long-term opioids, and larger trials of behavioral and exercise/movement interventions for pain among patients with substance use disorders.