Highlights•Rural residence is protective of experiencing a hospitalization for both HIV and opioid-related conditions.•Residents of the Northeast were 2.5 times more likely to be hospitalized for co-occurring HIV and opioid when compared to residents of the Midwest.•Patients which were identified as White, or Black were more likely than other races to experience hospitalizations for both HIV and opioid-related conditions.•Patients with no insurance, Medicaid, or other public coverages were more likely than privately insured patients to be hospitalized for co-occurring HIV and opioid-related conditions.