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Drug use-associated infective endocarditis (DUA-IE) is a major cause of illness and death for people with substance use disorder (SUD). Investigations to date have largely focused on advancing the care of patients with DUA-IE and included drug use disorder treatment, decisions about surgery, and choice of antibiotics during the period of hospitalization. Transitions from hospital to outpatient care are relatively unstudied and frequently a key factor of uncontrolled infection, continued substance use, and death. In this paper, we review the evidence supporting cross-disciplinary care for people with DUA-IE and highlight domains that need further clinician, institutional, and research investment in clinicians and institutions. We highlight best practices for treating people with DUA-IE, with a focus on addressing health disparities, meeting health-related social needs, and policy changes that can support care for people with DUA-IE in the hospital and when transitioning to the community., Competing Interests: Funding Support and Author Disclosures Dr Schranz is supported by the National Institute on Drug Abuse (K23DA049946). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)