Importance:  At least 500 000 people in the US experience homelessness nightly. More than 30% of people experiencing homelessness also have a substance use disorder. Involuntary displacement is a common practice in responding to unsheltered people experiencing homelessness. Understanding the health implications of displacement (e.g., “sweeps,” “clearings,” “cleanups”) is important, especially as they relate to key substance use disorder outcomes.

Objective:  To estimate the long-term health effects of involuntary displacement of people experiencing homelessness who inject drugs in 23 US cities.

Design, Setting, and Participants:  A closed cohort microsimulation model that simulates the natural history of injection drug use and health outcomes among people experiencing homelessness who inject drugs in 23 US cities. The model was populated with city-level data from the Centers for Disease Control and Prevention’s National HIV Behavioral Surveillance system and published data to make representative cohorts of people experiencing homelessness who inject drugs in those cities.

Main Outcomes and Measures:   Projected outcomes included overdose mortality, serious injection–related infections and mortality related to serious injection–related infections, hospitalizations, initiations of medications for opioid use disorder, and life-years lived over a 10-year period for 2 scenarios: “no displacement” and “continual involuntary displacement.” The population-attributable fraction of continual displacement to mortality was estimated among this population.

Results:  Models estimated between 974 and 2175 additional overdose deaths per 10 000 people experiencing homelessness at 10 years in scenarios in which people experiencing homelessness who inject drugs were continually involuntarily displaced compared with no displacement. Between 611 and 1360 additional people experiencing homelessness who inject drugs per 10 000 people were estimated to be hospitalized with continual involuntary displacement, and there will be an estimated 3140 to 8812 fewer initiations of medications for opioid use disorder per 10 000 people. Continual involuntary displacement may contribute to between 15.6% and 24.4% of additional deaths among unsheltered people experiencing homelessness who inject drugs over a 10-year period.

Conclusion and Relevance:   Involuntary displacement of people experiencing homelessness may substantially increase drug-related morbidity and mortality. These findings have implications for the practice of involuntary displacement, as well as policies such as access to housing and supportive services, that could mitigate these harms.