Background: North America and other parts of the globe are in the midst of a public health emergency related to opioid overdoses and a highly contaminated illicit drug supply. Unfortunately, there is a substantial gap in our understandings about how this crisis affects key populations not conventionally identified within overdose-related surveillance data. This gap is particularly pronounced for gay, bisexual, and other men who have sex with men (sexual minority men)-a population that experiences substance use-related inequities across adolescence and young adulthood. Methods: We draw on in-depth semi-structured interviews conducted in 2018 with a diverse sample (N = 50) of sexual minority men ages 15-30 who use substances and live in Vancouver, Canada, to identify how patterns and contexts of substance use are occurring in the context of the opioid overdose crisis. Results: Our analysis revealed three themes: awareness, perceptions, and experiences of risk; strategies to mitigate risk; and barriers to safer substance use. First, participants described how they are deeply impacted by the contaminated illicit drug supply, and how there is growing apprehension that fatal and non-fatal overdose risk is high and rising. Second, participants described how procuring substances from "trustworthy" drug suppliers and other harm reduction strategies (e.g., drug checking technologies, Naloxone kits, not using alone) could reduce overdose risk. Third, participants described how interpersonal, service-related, and socio-structural barriers (e.g., drug criminalization and the lack of a regulated drug supply) limit opportunities for safer substance use.