Objectives: Most low-income countries are characterized by poor health infrastructures and lack systems needed to timely detect and control disease outbreaks, such as the 2014-16 Ebola Viral Disease and COVID-19. In such contexts, a “One Health” approach, which involves investing in both human and animal health systems, plausibly improves local health outcomes by enabling early detection of zoonotic diseases before they are transmitted to humans, and by timely triggering a health system response needed to mitigate possible outbreaks. There is an urgent call to translate One Health into action and create inclusive and sustainable policies. There is, however, little direct evidence on the gains from One Health approaches. We contribute here by using a randomised intervention to assess the impact of a participatory community-based One Health program. Evidence before this study: A 2016 systematic review searched Scopus, PubMed, and ISI Web of Science using the term “One Health”, restricting publication date between 2003 and 2015.1 The search yielded 1,839 unique articles, but only four evaluated a One Health intervention using quantitative metrics. We performed the same search on 10 April 2023. Reflecting the burgeoning interest in One Health, we found an additional 9,715 unique articles. In total, only 17 articles, however, evaluated a One Health intervention implemented in real-world settings, utilizing quantitative metrics. Furthermore, these studies did not employ experimental methods to assess impact, relied on datasets with often only few observations, and focused exclusively on disease incidence. In the Supplementary Material (Appendix A), we provide a flowchart of the literature review and summarize these 17 related studies. Contribution: This study is the first cluster-randomised trial to assess the impact of a participatory community-based intervention establishing local health platforms employing a One Health approach. We evaluate the intervention at scale and explore the impact of the program on human health, but also on key intermediary outcomes like animal health and animal and human health behaviours. Design: Cluster-randomised control trial. Setting: 363 villages in rural Sierra Leone Participants: The Sierra Leone government and communities recruited, trained and installed Community Animal Health Workers (CAHWs) to work alongside Community Health Workers (CHWs) in 300 randomly selected rural villages in Sierra Leone. Another 63 villages were randomly selected as control sites and had CHWs exclusively. CAHWs provided essential animal health services, disseminated information regarding animal and human health best practices, and actively participated in surveillance efforts by reporting suspected disease symptoms to government supervisors. Main outcome measures: Survey based measures of human health, as well as key intermediary outcomes; including animal health, animal and human health-related behaviours, integration into public services, and household wealth. Results: In July and August 2017, the community-based One Health program successfully recruited, trained and installed CAHWs across 287 villages. Throughout the program's duration, spanning from July 2017 to July 2019, the CAHWs reported on 19,283 suspected disease-related events. Using survey data from over 2,500 respondents, collected in March and April 2020, we found no evidence for impacts on human health (-0.008 Standard Deviation Units (SDU), 95% CI -0.148, 0.133). The program did however significantly improve core intermediary outcomes, including animal health (0.164 SDU, 95% CI 0.017, 0.311), animal husbandry practices (0.255 SDU, 95% CI 0.087, 0.424), human health behaviours (0.187 SDU, 95% CI 0.025, 0.348), integration into public services (0.339 SDU, 95% CI 0.137, 0.541), and household wealth (0.163 SDU, 95% CI 0.053, 0.273). Conclusions: Participatory community-based One Health interventions can serve as a guide for policymakers that seek to strengthen the national health systems by improving disease surveillance and preventative practices that are expected to increase health security nationally and globally. More research is needed to understand how the magnitude, modality, and timing of the program and background conditions may shape program impact on human health. Trial registration: The trial was registered at the National Trail Registry (#21660), which is part of the ICTRP, and OSF (https://osf.io/9xfv3).