ImportanceTraumatic injury is a major cause of morbidity for people experiencing homelessness (PEH). However, injury patterns and subsequent hospitalization among PEH have not been studied on a national scale.ObjectiveTo evaluate whether differences in mechanisms of injury exist between PEH and housed trauma patients in North America and whether the lack of housing is associated with increased adjusted odds of hospital admission.Design, Setting, and ParticipantsThis was a retrospective observational cohort study of participants in the 2017 to 2018 American College of Surgeons’ Trauma Quality Improvement Program. Hospitals across the US and Canada were queried. Participants were patients aged 18 years or older presenting to an emergency department after injury. Data were analyzed from December 2021 to November 2022.ExposuresPEH were identified using the Trauma Quality Improvement Program’s alternate home residence variable.Main Outcomes and MeasuresThe primary outcome was hospital admission. Subgroup analysis was used to compared PEH with low-income housed patients (defined by Medicaid enrollment).ResultsA total of 1 738 992 patients (mean [SD] age, 53.6 [21.2] years; 712 120 [41.0%] female; 97 910 [5.9%] Hispanic, 227 638 [13.7%] non-Hispanic Black, and 1 157 950 [69.6%] non-Hispanic White) presented to 790 hospitals with trauma, including 12 266 PEH (0.7%) and 1 726 726 housed patients (99.3%). Compared with housed patients, PEH were younger (mean [SD] age, 45.2 [13.6] years vs 53.7 [21.3] years), more often male (10 343 patients [84.3%] vs 1 016 310 patients [58.9%]), and had higher rates of behavioral comorbidity (2884 patients [23.5%] vs 191 425 patients [11.1%]). PEH sustained different injury patterns, including higher proportions of injuries due to assault (4417 patients [36.0%] vs 165 666 patients [9.6%]), pedestrian-strike (1891 patients [15.4%] vs 55 533 patients [3.2%]), and head injury (8041 patients [65.6%] vs 851 823 patients [49.3%]), compared with housed patients. On multivariable analysis, PEH experienced increased adjusted odds of hospitalization (adjusted odds ratio [aOR], 1.33; 95% CI, 1.24-1.43) compared with housed patients. The association of lacking housing with hospital admission persisted on subgroup comparison of PEH with low-income housed patients (aOR, 1.10; 95% CI, 1.03-1.19).Conclusions and RelevanceInjured PEH had significantly greater adjusted odds of hospital admission. These findings suggest that tailored programs for PEH are needed to prevent their injury patterns and facilitate safe discharge after injury.