Although the global burden of HIV infection among sex workers (SW) has been well recognized, HIV-related risks among sex workers who inject drugs (SW-IDU) have received less attention. We investigated the relationship between sex work and HIV incidence among people who inject drugs (IDU) in a Canadian setting.Prospective cohort study.Using Kaplan-Meier methods and the extended Cox regression, we compared HIV incidence among SW-IDU and non-SW-IDU in Vancouver, Canada, after adjusting for potential confounders.Between 1996 and 2012, 1647 participants were included in the study, including 512 (31.1%) IDU engaged in sex work. At 5 years the HIV cumulative incidence was higher among SW-IDU in comparison to other IDU (12 vs. 7%, P = 0.001). In unadjusted Cox regression analyses, HIV incidence among SW-IDU was also elevated [relative hazard: 1.69; 95% confidence interval (CI): 1.13-2.53]. However, in a multivariable analysis, sex work did not remain associated with HIV infection (adjusted relative hazard: 0.74; 95% CI: 0.45-1.20), with cocaine injection appearing to account for the elevated risk for HIV infection among SW-IDU.These data suggest that local SW-IDU have elevated rates of HIV infection. However, our exploration of risk factors among SW-IDU demonstrated that drug use patterns and environmental factors, rather than sexual risks, may explain the elevated HIV incidence among SW-IDU locally. Our findings highlight the need for social and structural interventions, including increased access to harm reduction programs and addiction treatment.