Background and aims: The full burden of the opioid epidemic on US hospitals has not been described. We aimed to estimate how heroin (HOD) and prescription opioid (POD) overdose-associated admissions, costs, outcomes and patient characteristics have changed from 2001 to 2012.

Design: Retrospective cohort study of hospital admissions from the National Inpatient Sample (NIS).

Setting: United States of America.

Participants: Hospital admissions in patients aged 18 years or older admitted with a diagnosis of HOD or POD. The NIS sample included 94 492 438 admissions from 2001 to 2012. The final unweighted study sample included 138 610 admissions (POD: 122 147 and HOD: 16 463).

Measurements: Primary outcomes were rates of admissions per 100 000 people using US Census Bureau annual estimates. Other outcomes included in-patient mortality, hospital length-of-stay, cumulative and mean hospital costs and patient demographics. All analyses were weighted to provide national estimates.

Findings: Between 2001 and 2012, an estimated 663 715 POD and HOD admissions occurred nation-wide. HOD admissions increased 0.11 per 100 000 people per year [95% confidence interval (CI) = 0.04, 0.17], while POD admissions increased 1.25 per 100 000 people per year (95% CI = 1.15, 1.34). Total in-patient costs increased by $4.1 million dollars per year (95% CI = 2.7, 5.5) for HOD admissions and by $46.0 million dollars per year (95% CI = 43.1, 48.9) for POD admissions, with an associated increase in hospitalization costs to more than $700 million annually. The adjusted odds of death in the POD group declined modestly per year [odds ratio (OR) = 0.98, 95% CI = 0.97, 0.99], with no difference in HOD mortality or length-of-stay. Patients with POD were older, more likely to be female and more likely to be white compared with HOD patients.

Conclusions: Rates and costs of heroin and prescription opioid overdose related admissions in the United States increased substantially from 2001 to 2012. The rapid and ongoing rise in both numbers of hospitalizations and their costs suggests that the burden of POD may threaten the infrastructure and finances of US hospitals.