The murder of George Floyd in 2020 spurred an outpouring of calls for racial justice in the United States, including within academic medicine. In response, academic health centers announced new antiracism initiatives and expanded their administrative positions related to diversity, equity, and/or inclusion (DEI). To understand the experiences of DEI leaders at US allopathic medical schools and academic health centers, ie, the structure of their role, official and unofficial responsibilities, access to resources, institutional support, and challenges. This qualitative study used key informant interviews with participants who held formal DEI positions in their school of medicine, health system, or department. Interviews were conducted from December 2020 to September 2021. Transcripts were coded using a phenomenographic approach, with iterative concurrent analysis to identify thematic categories across participants. Data were analyzed from January to December 2021. Formal DEI role. Questions elicited reflection on the responsibilities of the role and the strengths and challenges of the unit or office. A total of 32 participants (18 of 30 [56%] cisgender women; 16 [50%] Black or African American, 6 [19%] Latinx or Hispanic, and 8 [25%] White) from 27 institutions with a mean (range) of 14 (3-43) years of experience in medical education were interviewed. More than half held a dean position (17 [53%]), and multiple participants held 2 or more titled DEI roles (4 [13%]). Two-thirds self-identified as underrepresented in medicine (20 [63%]) and one-third as first generation to attend college (11 [34%]). Key themes reflected ongoing challenges for DEI leaders, including (1) variability in roles, responsibilities, and access to resources, both across participants and institutions as well as within the same position over time; (2) mismatch between institutional investments and directives, including insufficient authority, support staff, and/or funding, and reduced efficacy due to lack of integration with other units within the school or health system; (3) lack of evidence-based practices, theories of change, or standards to guide their work; and (4) work experiences that drive and exhaust leaders. Multiple participants described burnout due to increasing demands that are not met with equivalent increase in institutional support. In this qualitative study, DEI leaders described multiple institutional challenges to their work. To effectively address stated goals of DEI, medical schools and academic centers need to provide leaders with concomitant resources and authority that facilitate change. Institutions need to acknowledge and implement strategies that integrate across units, beyond one leader and office. Policymakers, including professional organizations and accrediting bodies, should provide guidance, accountability mechanisms, and support for research to identify and disseminate evidence for best practices. Creating statements and positions, without mechanisms for change, perpetuates stagnation and injustice.