George Karandinos, MD, PhD

Severe infections linked to opioid use often progress rapidly, particularly when access to timely medical care is limited. This can result in devastating health outcomes, including life-altering amputations. While clinicians and local researchers have reported rising numbers of amputations among people who use opioids, national data describing long-term trends has been limited.

A study led by George Karandinos, MD, PhD, at Mass General Brigham and Daniel Ciccarone, MD, MPH, at the University of California San Francisco examined U.S. hospitalizations from 2016–2022 to better understand how amputation rates have shifted over time and across regions.

The study found that during this period, amputation rates increased among both opioid- and non-opioid-related hospitalizations, but the rise was significantly steeper among opioid-related cases—especially in the Northeast and Western United States. Opioid-related amputations were also more likely to involve higher anatomical levels, such as above the knee or the upper extremities, while non-opioid-related amputations more often involved toes or parts of the foot.

The authors note that several factors may be contributing to these trends, including changes in the illicit drug supply. The growing presence of xylazine, which is associated with severe tissue damage and hard-to-treat wounds, may play an important role, though amputation rates also increased in areas where xylazine was not prevalent during the study period. At the same time, broader structural factors such as delayed care, limited access to wound treatment and housing instability are likely contributors.

Overall, the findings highlight a growing burden of severe, yet often preventable, harm among people using opioids and underscore the need for earlier intervention.

Published in Annals of Internal Medicine on May 5, 2026 | Read the paper: “Amputation Rates Among Opioid Related Hospitalizations in the U.S., 2016–2022”

Summary reviewed by: George Karandinos, MD, PhD, lead author