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As the opioid epidemic progresses, a better understanding of those at elevated risk of opioid overdose is needed, particularly for populations whose growing risk may be overlooked. Medicare recipients under age 65 (Medicare-disability beneficiaries [MDBs]) are one such population. We sought to analyze characteristics of opioid-overdose hospitalizations among MDBs and quantify the contribution of this population to opioid-overdose hospitalizations overall.This retrospective cohort study included patients hospitalized for opioid overdose in the National/Nationwide Inpatient Sample from 1998 to 2013. The primary outcome measurements were number and characteristics of discharges, including patient sex, age, race, prescription opioid versus heroin overdose, and comorbidities.MDBs constituted 11.7% of US opioid overdose hospitalizations among those under 65 years of age in 1998; this proportion grew to 24.5% by 2013 (P< .0001). The proportion of female patients grew markedly among this cohort (P< .0001) and were disproportionately represented among MDBs (P< .0001). Prescription opioid overdose accounted for a larger proportion of opioid overdose hospitalizations among MDBs than among non-Medicare-insured patients under 65 years old (P< .0001). MDBs generally exhibited greater comorbidity burden versus non-Medicare-insured patients under age 65; however, chronic drug and alcohol abuse were less commonly documented among the Medicare cohort (P< .0001).MDBs constitute a substantial and growing proportion of opioid overdose hospitalizations in the United. To prevent opioid overdoses among MDBs, care must be taken to address the unique needs of this population.