SUMMARY The success of the High Plains Intermountain Center for Agricultural Health and Safety (HICAHS) is grounded in engaging and listening to stakeholders and responding to regional needs with sound and relevant programs and partnerships. Building on a substantial record of accomplishments in research, intervention, education and outreach, we propose an innovative transdisciplinary Center that leverages expertise and resources among partners to promote a healthy agricultural and forestry/logging population in PHS Region VIII (Colorado, Montana, North Dakota, South Dakota, Utah, and Wyoming) and beyond. Over the past 6 years we have fostered a One Health approach with the rapidly expanding dairy industry in our region, responded to the disproportionate COVID-19 impacts on agricultural workers, and strengthened partnerships in occupational safety with the logging industry in Montana. This proposal brings together an internationally recognized leadership team, outstanding new investigators, and a well-developed regional partnership to address the new and unique needs of this region. Building on the Regional Needs Assessment and following diversity, equity, and inclusion principles, we will continue to advance health and safety in the region. The Mission of HICAHS is to improve the health and well-being of workers in food, fiber, and timber production by engaging partners in transdisciplinary research, education, and prevention programs across the region. The Center’s long-term goal is to reduce the risk of work-related injuries, fatalities, and illnesses primarily in the agriculture and forestry subsectors in the region. We propose integrating new and existing knowledge and using multiple routes of dissemination to translate research into improved agricultural health and safety practices through our three Cores: 1. Evaluation & Planning Core; 2. Research Core including our Pilot/Feasibility Program, two Basic/Etiological Research projects, one Intervention Research project, and one Translation Research project; 3. Outreach Core including our Community-Initiated Grant Program. By achieving our aims, we expect an effective Center infrastructure, cohesive and complementary research and outreach efforts, and strengthened partnerships among researchers and practitioners working together to support the agricultural and forestry workforce. Ultimately, we expect our work to contribute to the reduction of risks of work-related injuries, fatalities, and illnesses and usher in our vision of a healthy and safe agriculture and forestry workforce in the HICAHS region and beyond.