IMPORTANCE: The burden of dental caries in remote Indigenous communities in Australia is unacceptably high. OBJECTIVES: We tested the impact of an annual caries preventive intervention, delivered by a fly-in/fly-out professional team, on Indigenous children residing in a remote Australian community, involving selective fissure sealants, topical povidone iodine and fluoride varnish application. The outcome was caries increment at 12- and 24-month follow-up. DESIGN, SETTING, PARTICIPANTS: Around 600 Indigenous children aged 5 to 17 years were invited to participate at baseline, of which 408 had caregiver consent provided. Of these, 196 consented to both the study and the treatment arm and comprised the experimental group. Two hundred and twelve consented to the epidemiological examination only, and constituted the comparison group. INTERVENTION: The Big Bang intervention, which occurred annually, comprised placement of fissure sealants, and application of povidone-iodine and fluoride varnish, following completion of each childs dental treatment plan. Standard diet and oral hygiene advice was provided. MAIN OUTCOMES AND MEASURES: Caries increment (number of tooth surfaces with new dental caries) in both primary and permanent dentitions at 12- and 24-month follow-up. RESULTS: At 12-month follow-up, children in the experimental group had, on average, 5.05 (5.47) new carious lesions compared to 7.49 (6.94) in the comparison group (p=0.001). The preventive fraction was 33%. At 24-month follow-up, children in the experimental group had, on average, 6.47 (6.07) new carious lesions compared to 8.43 (5.83) in the comparison group (p=0.002). The preventive fraction was 23%. CONCLUSIONS AND RELEVANCE: Indigenous children exposed to the Big Bang caries intervention had significantly less increment in dental disease than those not exposed to the intervention. Benefits were demonstrated at both 12- and 24-month follow-ups, suggesting that the intervention is likely to be sustained if delivered across a childs life. The cost-effectiveness of this approach is being evaluated.