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Results The annual age-adjusted death rates for drug overdose deaths that involved any opioid significantly increased for all racial/ethnic groups in metropolitan and non-metropolitan areas from 1999 to 2017. The largest average annual increases in rates occurred among non-Hispanic whites in non-metropolitan areas (13.6% increase per year) and medium-small metropolitan areas (12.3% increase per year), followed by non-Hispanic blacks in medium-small metropolitan areas (11.3% increase per year). Conclusions The variations in opioid-invol