Opioid use disorder (OUD) and opioid overdose deaths (OODs) are prevalent among US workers, but work-related factors have not received adequate attention as either risk factors or opportunities for OOD prevention. Higher prevalence of OOD in those with heavy physical jobs, more precarious work, and limited health care benefits suggest work environment and organizational factors may predispose workers to the development of OUD.Organizational policies that reduce ergonomic risk factors, respond effectively to employee health and safety concerns, provide access to nonpharmacologic pain management, and encourage early substance use treatment are important opportunities to improve outcomes. Organizational barriers can limit disclosure of pain and help-seeking behavior, and opioid education is not effectively integrated with workplace safety training and health promotion programs.Policy development at the employer, government, and association levels could improve the workplace response to workers with OUD and reduce occupational risks that may be contributing factors.