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We report the experience of a multidisciplinary team at a health organization in Vancouver, Canada, working to characterize the incidence, patient and healthcare provider perspectives, and overall impact of self-injecting non-prescribed substances into vascular access devices (SIVAD). The case study of SIVAD begins with a patient’s perspective, including patient rationale for SIVAD, understanding of risks and the varying responses given by healthcare providers following disclosure of SIVAD. Using the limited literature available on the subject, we summarize the intersection of SIVAD and substance use and outline known and anticipated health risks. The case study is further contextualized by experience from a Vancouver in-hospital Overdose Prevention Site (OPS), where 37% of all individual visits involve SIVAD. The case study concludes by describing the systematic process by which local clinical guidance for SIVAD harm reduction was developed with stakeholder engagement, medical ethics consultation, expert consensus guideline development and implementation with staff education and planned research evaluation.