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Objective: Injection drug use (IDU) is prevalent in North America and is associated with presentations with infective endocarditis. Supporting patients who present with infective endocarditis related to IDU through harm reduction, a pragmatic approach to reduce secondary harms of a health behavior, helps address the underlying IDU. We share a case exemplar of how one acute care facility integrated harm-reduction practices into daily patient care. Methods: We took a 3-stage approach to integrate harm-reduction practices into daily patient care. In stage 1, we raised awareness and knowledge of harm reduction through education. In stage 2, we provided explicit support for harm reduction. In stage 3, we provided tangible tools to support harm reduction. Results: More than 300 staff attended education sessions and reported increased knowledge related to substances, harm reduction, and engaging patients who use substances in conversations. Staff requested the hospital explicitly support harm reduction, which led to stage 2. The creation of a harm-reduction philosophy statement provided permission to engage in harm-reduction practices. Stage 3 included the creation of a harm-reduction supply distribution program and consultations with Addictions Medicine and treatment programs. The implementation of harm-reduction supply distribution was successful and is being spread across the facility. Conclusions: Engaging in harm-reduction practices within an acute care facility is possible through a multistage process focused on education, explicit support, and tangible tools. Spreading harm-reduction integration and working with patients who used substances to evaluate effectiveness are key next steps.