We conducted a 3-year cost-effectiveness analysis on the cavitated dentine carious lesion preventive capabilities of composite resin (CR) (reference group) and atraumatic restorative treatment (ART) high-viscosity glass-ionomer cement (HVGIC) sealants compared to supervised toothbrushing (STB) in high-risk first permanent molars. School children aged 6-7 years in 6 schools (2 per group) received CR and ART/HVGIC sealants or STB daily for 180 days each school year. Data were collected prospectively and cost estimates were made for sample data and a projection of 1,000 sealants/STB high-risk permanent molars. Although STB had the best outcome, its high implementation cost (95% of cost for supervisors visiting schools 180 days/school year) affected the results. ART/HVGIC was cost-effective compared to CR for the sample data (savings of USD 37 per cavitated dentine carious lesion prevented), while CR was cost-effective compared to ART/HVGIC for the projection (savings of USD 17 per cavitated dentine carious lesion prevented), and both were cost-saving compared to STB. Two STB scenarios were tested in sensitivity analyses with variations in caries incidence and number of supervision days; results showed STB had lower costs and higher savings per cavitated dentine carious lesion prevented than CR and ART/HVGIC. A major assumption is that both scenarios have the same high effectiveness rate experienced by STB under study conditions; however, they point to the value of further research on the benefits of adopting STB as a long-term venture in a general population of school children.