BACKGROUND: The oral health of Indigenous children in remote communities is much worse than other population groups in Australia. Providing and maintaining an oral health service is challenging due to the remoteness of communities, the associated high cost, and the low retention of clinical staff. An annual preventive intervention delivered by fly-in clinicians may be a more cost-effective way to manage this problem. In this analysis we estimate the cost-effectiveness of an annual professional intervention for the prevention of dental caries in children of a remote Indigenous community in Far North Queensland. METHODS: A cost-effectiveness analysis was conducted based on an annual preventive intervention protocol. This included treating all dental decay in those with disease, applying fissure sealants, a disinfectant swab, fluoride varnish and providing oral hygiene instructions and dietary advice to all participating school children. This study included an intervention group and a natural comparison group and both groups were followed-up for 2 years after the initial preventive intervention. A Markov model was built to assess the cost-effectiveness of the intervention compared with the usual care. Costs of treatment from the Queensland Department of Health were used and effectiveness was measured as quality-adjusted life years (QALYs) with the CHU-9D. One-way and probabilistic sensitivity analyses were conducted to identify key drivers and quantify uncertainty. RESULTS: The preventive intervention was found to be highly cost-effective. The incremental cost per QALY gained was AU$3747. Probability of new caries and seeking treatment were identified as the main drivers of the model. In probabilistic sensitivity analysis intervention was cost effective in 100% of simulations. CONCLUSION: An annual preventive intervention for remote Indigenous communities in Australia is a highly cost-effective strategy to prevent dental caries and improve the quality of life of children.