STUDY OBJECTIVE: We describe the prevalence, trends, and factors associated with repeated emergency department (ED) encounters for opioid usage across multiple, independent hospital systems. METHODS: A statewide regional health information exchange system provided ED encounters from 4 Indiana hospital systems for 2012 to 2017. In accordance with a series of International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 diagnosis codes for opioid abuse, adverse effects of opioids, opioid dependence and unspecified use, and opioid poisoning, we identified patients with an ED encounter associated with opioid usage (9,295 individuals; 12,642 encounters). Multivariate logistic regression models then described the patient, encounter, prescription history, and community characteristics associated with the odds of a patient's incurring a subsequent opioid-related ED encounter. RESULTS: The prevalence of repeated nonfirst opioid-related ED encounters increased from 9.0% of all opioid encounters in 2012 to 34.3% in 2017. The number of previous opioid-related ED encounters, unique institutions at which the individual had had encounters, the encounter's being heroin-related, the individual's having a benzodiazepine prescription filled within 30 days before the encounter, and being either Medicaid insured or uninsured compared with private insurance were associated with significantly greater odds of having a subsequent encounter. CONCLUSION: The ED is increasingly a site utilized as the setting for repeated opioid-related care. Characteristics of the individual, encounter, and community associated with repeated opioid-related encounters may inform real-time risk-prediction tools in the ED setting. Additionally, the number of institutions to which the individual has presented may suggest the utility of health information exchange data and usage in the ED setting.