Illicit opioid use in Canada and elsewhere increasingly involves a variety of opioids and non-injection routes of administration. Injection and non-injection opioid users tend to differ in various key characteristics. From a public health perspective, non-injection routes of opioid use tend to be less harmful due to lesser morbidity and mortality risks. Our study compared current injectors (80%) and non-injectors (20%) in a multi-site sample of regular illicit opioid users from across Canada ('OPICAN' study). In bivariate analysis, injectors and non-injectors differed by prevalence in social and health characteristics as well as drug use. Logistic regression analysis identified city, drug use, housing status and mental health problems as independent predictors of injection status. Further analysis revealed that the majority of current non-injectors had an injection history. Our results reinforce the need to explore potential interventions aimed at preventing the transition from non-injectors to injecting, or facilitating the transition of injectors to non-injecting, as initiated in several other contexts.