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During the COVID-19 vaccination rollout from March 2021- December 2022, the Centers for Disease Control and Prevention funded 110 primary and 1051 subrecipient partners at the national, state, local, and community-based level to improve COVID-19 vaccination access, confidence, demand, delivery, and equity in the United States. The partners implemented evidence-based strategies among racial and ethnic minority populations, rural populations, older adults, people with disabilities, people with chronic illness, people experiencing homelessness, and other groups disproportionately impacted by COVID-19. CDC also expanded existing partnerships with healthcare professional societies and other core public health partners, as well as developed innovative partnerships with organizations new to vaccination, including museums and libraries. Partners brought COVID-19 vaccine education into farm fields, local fairs, churches, community centers, barber and beauty shops, and, when possible, partnered with local healthcare providers to administer COVID-19 vaccines. Inclusive, hyper-localized outreach through partnerships with community-based organizations, faith-based organizations, vaccination providers, and local health departments was critical to increasing COVID-19 vaccine access and building a broad network of trusted messengers that promoted vaccine confidence. Data from monthly and quarterly REDCap reports and monthly partner calls showed that through these partnerships, more than 295,000 community-level spokespersons were trained as trusted messengers and more than 2.1 million COVID-19 vaccinations were administered at new or existing vaccination sites. More than 535,035 healthcare personnel were reached through outreach strategies. Quality improvement interventions were implemented in healthcare systems, long-term care settings, and community health centers resulting in changes to the clinical workflow to incorporate COVID-19 vaccine assessments, recommendations, and administration or referrals into routine office visits. Funded partners' activities improved COVID-19 vaccine access and addressed community concerns among racial and ethnic minority groups, as well as among people with barriers to vaccination due to chronic illness or disability, older age, lower income, or other factors., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jane R. Nilson reports a relationship with Astrazeneca (AZN), Amcor (AMCR), and Organon (OGN) and Mutual fund Eventide Healthcare and Life Fund that includes: equity or stocks. Sara Adelsberg, Theresa Bailey, Alexa Frank, and Claire Perkins: CDC has contracted with Deloitte Consulting, LLP, since December 2019 to support CDC’s Immunization Services Division in developing, standing up, and implementing a comprehensive, multi-faceted program focused on reducing racial and ethnic disparities in adult immunization. Deloitte Consulting, LLP, is a large organization that receives funding from many organizations and agencies. CDC funded a number of activities implemented by Deloitte and others. These authors do not have any reason to believe that any activities beyond those included in this support have any material relationship to this manuscript. Elizabeth Sobczyk: serves on an advisory committee for Sanofi Pasteur related to pertussis, separate from her time with AMDA. Julie Zajac: served on the Cooperative Extension System’s Health Innovation Task Force from March 2020 to March 2022. Since December 2022, she has served on the Extension Foundation’s Health Leadership Committee., (Published by Elsevier Ltd.)