AbstractBackgroundGlobally, children’s caries prevalence exceeds 30% and has not markedly changed in 30 years. School-based caries prevention programs may be an effective method to reduce caries prevalence, obviate traditional barriers to care, and use aerosol-free interventions. The objective of this study was to explore the clinical effectiveness of a comprehensive school-based, aerosol-free, caries prevention program.MethodsWe 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 generalized estimating equations to estimate the change in the prevalence of untreated caries over time.ResultsThe prevalence of untreated caries decreased by greater than 50%: from 39% to 18% in phase 1, and from 28% to 10% in phase 2. The per-visit adjusted odds ratio of untreated decay was 0.79 (95% CI: 0.73, 0.85).Conclusions and Practical ImplicationsWe show that a school-based comprehensive caries prevention program was associated with substantial reductions in children’s caries, supporting the concept of expanding traditional practices to include office- and community-based aerosol-free care.