BackgroundStreet-involved youth who use illicit drugs are at high risk for health-related harms; however, the profile of youth at greatest risk of hospitalization has not been well described. We sought to characterize hospitalization among street-involved youth who use illicit drugs and identify the most frequent medical reasons for hospitalization among this population.MethodsFrom January 2005 to May 2016, data were collected from the At-Risk Youth Study (ARYS), a prospective cohort study of street-involved youth in Vancouver, Canada. Multivariable generalized estimating equation (GEE) was used to identify factors associated with hospitalization.ResultsAmong 1216 participants, 373 (30.7%) individuals reported hospitalization in the previous 6 months at some point during the study period. The top three reported medical reasons for hospital admission were the following: mental illness (37.77%), physical trauma (12.77%), and drug-related issues (12.59%). Factors significantly associated with hospitalization were the following: past diagnosis of a mental illness (adjusted odds ratio [AOR] = 1.85; 95% confidence interval [95% CI] 1.47–2.33), frequent cocaine use (AOR = 2.15; 95% CI 1.37–3.37), non-fatal overdose (AOR = 1.76; 95% CI 1.37–2.25), and homelessness (AOR = 1.40; 95% CI 1.16–1.68) (all p < 0.05).ConclusionsFindings suggest that mental illness is a key driver of hospitalization among our sample. Comprehensive approaches to mental health and substance use in addition to stable housing offer promising opportunities to decrease hospitalization among this vulnerable population.