<br><i>Objective</i>: This study examined whether childhood sexual abuse predicts initiation of injection drug use in a prospective cohort of youth. <i>Method</i>: From October 2005 to November 2010, data were collected from the At Risk Youth Study (ARYS), a prospective cohort study of street-involved youth in Vancouver, Canada. Inclusion criteria were age 14–26 years, no lifetime drug injection, and non-injection drug use in the month preceding enrollment. Participants were interviewed at baseline and semiannually thereafter. Cox regression was employed to identify risk factors for initiating injection. <i>Results</i>: Among 395 injection-naïve youth, 81 (20.5%) reported childhood sexual abuse. During a median follow-up of 15.9 months (total follow-up 606.6 person-years), 45 (11.4%) youth initiated injection drug use, resulting in an incidence density of 7.4 per 100 person-years. In univariate analyses, childhood sexual abuse was associated with increased risk of initiating injection (unadjusted hazard ratio [HR], 2.38; 95% confidence interval [CI], 1.29–4.38; p=0.006), an effect that persisted in multivariate analysis despite adjustment for gender, age, aboriginal ancestry and recent non-injection drug use (adjusted HR, 2.71; 95% CI, 1.42–5.20; p=0.003). <i>Conclusion</i>: Childhood sexual abuse places drug users at risk for initiating injection. Addiction treatment programs should incorporate services for survivors of childhood maltreatment.