BackgroundYouth substance use programming and educational strategies are frequently informed by prevention approaches that emphasize abstinence goals, which often do not resonate with youth in their lack of acknowledgment of young people’s social context and how young people perceive positive effects of substance use. Further, approaches to drug prevention have been critiqued as adopting a one-size-fits-all approach and therefore inadequate in addressing substance use in the context of population variation and inequities. In response to the limitations of current approaches to prevention, programming informed by harm reduction principles that aims to minimize harms without requiring abstinence is emergent in school settings. However, youth perspectives informing harm reduction are limited in both research and program development.MethodsThis paper draws on data from the Researching Adolescent Distress and Resilience (RADAR) study, which utilized an ethnographic approach to bring youth voice to the literature on mental health and substance use. Qualitative data collection included individual interviews (n = 86) with young people aged 13–18 across three communities—representing urban, suburban, and rural geographies—in British Columbia, Canada. A multi-site qualitative analysis of interview data was conducted to identify themes across and within each research site.ResultsAcross all three sites, young people’s individual experiences of substance use were shaped by geographic, socio-cultural, and political contexts, with youth describing their use in relation to the nature of substance use in peer groups and in the broader community. To manage their own substance use and reduce related harms, youth employed a variety of ad hoc harm minimization strategies that were reflective of their respective contexts.ConclusionsThe findings from this study suggest the importance of harm reduction approaches that are contextually relevant and responsive to the lived experiences of youth. Youth perspectives in the development of harm reduction programming are needed to ensure that approaches are relatable and meaningful to young people, and effective for promoting the minimization of substance-related harms.