Starting in 2007, a 2-year study based on ethnographic methodology was carried out downtown Montreal, Canada. A thematic analysis of observational and interview-based notes was conducted. Illicit prescription opioid (PO) use was widespread among streetbased participants. Injection was the main mode of PO administration observed among users. Some injection practices such as “doing a wash” could pose new challenges in terms of prevention of infections. More research is needed to examine the role of illicit PO use in the development of opiate addiction and to better understand drug-using contexts that put PO users at risk of infections. The study’s limitations are noted.