Guidelines recommend against initiating long-acting opioids during acute hospitalization, owing to higher risk of overdose and morbidity compared to short-acting opioid initiation. We investigated the incidence of long-acting opioid initiation following hospitalization in a retrospective cohort of Medicare beneficiaries with an acute care hospitalization in 2016 who were ≥65 years old, did not have cancer or hospice care, and had not filled an opioid prescription within the preceding 90 days. Among 258,193 hospitalizations, 47,945 (18.6%) were associated with a claim for a new opioid prescription in the week after hospital discharge: 817 (0.3%) with both short- and long-acting opioids, 125 (0.1%) with long-acting opioids only, and 47,003 (18.2%) with short-acting opioids only. Most long-acting opioid claims occurred in surgical patients (770 out of 942; 81.7%). Compared with beneficiaries prescribed short-acting opioids only, beneficiaries prescribed long-acting opioids were younger, had a higher prevalence of diseases of the musculoskeletal system and connective tissue, and had more known risk factors for opioid-related adverse events, including anxiety disorders, opioid use disorder, prior long-term high-dose opioid use, and benzodiazepine co-prescription. These findings may help target quality-improvement initiatives.