Background: Unchanged in 30 years, the global prevalence of dental caries is >35% in low-, middle-, and high-income countries. As proposed in the Lancet Series on Oral Health, reducing the caries burden requires a radical change from care that is high-tech, high-cost, low-access, office-based, interventional, and delivered by dentists, to care that is low-tech, low-cost, high-access, community-based, preventive, and delivered by non-dentists. Here we report on one test of the latter, community-based prevention delivered by non-dentists. Methods: We conducted a 6-year prospective open cohort study in 33 U.S. public elementary schools, providing care to 6,927 children in communities with and without water fluoridation. Following a dental examination, dental hygienists provided twice-yearly prophylaxis, glass ionomer sealants, glass ionomer interim therapeutic restorations, fluoride varnish, toothbrushes, fluoride toothpaste, oral hygiene instruction, and referral to community dentists as needed. We used a two-phase school enrollment with six initial schools, and 27 later. To estimate the change in prevalence of untreated decay over time we fit regression models by using generalized estimating equations. Findings: The prevalence of untreated caries decreased from 39% at baseline to 18% in the initial six schools, and from 28% to 10% in the remaining 27 schools. The per-visit reduction in the odds of decay mainly occurred in subjects with untreated decay at baseline (adjusted odds ratio 0.79, 95% confidence interval 0.73, 0.85). Interpretation: These results support the hypothesis that community-based, comprehensive caries prevention reduces caries prevalence. The study also demonstrates the feasibility of low-tech, prevention-focused models of care. Funding Statement: Multiple governmental and non-governmental organizations supported this work. Declaration of Interests: The following organizations provided partial support for this work: National Institute of Minorities and Health Disparities, the Dental Service of Massachusetts – DentaQuest, Bingham Trust, the Massachusetts State Legislature, the American Dental Trade Alliance, Belizekian Trust and Noonan, and Bank of America Trust. In-kind support included: glass ionomer provided by GC America and toothbrushes, fluoride toothpaste, and fluoride varnish provided by Colgate Palmolive. None of the preceding organizations or individuals working with or for them had any input into trial design, patient recruitment, clinical care, data collection, analysis, interpretation, report writing, or any aspect of the study. All authors were either compensated by grant funding or were uncompensated for this work. No commercial entity compensated any of the authors for conducting the study or drafting the manuscript. Ethics Approval Statement: The Forsyth Institute, Boston, MA Investigational Review Board approved this study. Reporting follows STROBE guidelines. The authors previously reported the study rationale, calibration, selection of protocols, interventions, and six-month preliminary outcomes. Informed consent and assent was obtained from guardians.