Introduction:An economic evaluation (EE) was conducted alongside a randomized controlled trial (the Protecting Teeth @ 3 Study [PT@3]), exploring the additional preventive value of fluoride varnish (FV) application at 6-monthly intervals in nursery schools compared to treatment as usual (TAU) in the same nurseries. TAU represented a multicomponent national child oral health improvement intervention, the Childsmile program, apart from nursery FV.Methods:The EE was a within-trial cost-utility analysis (CUA) comparing the FV and TAU groups. The CUA was conducted from a National Health Service perspective and followed relevant methods guidance. Within-trial costs included intervention costs and health care resource use costs. Health outcomes were expressed in quality-adjusted life years (QALYs) accrued over the 2-y follow-up period. The Child Health Utility 9 Dimensions questionnaire was used to obtain utility scores. National reference costs were used, a discount rate of 1.5% for public health interventions was adopted, multiple imputation methods for missing data were employed, sensitivity analyses were conducted, and incremental cost-utility ratios were calculated.Results:Data from 534 participants from the 2014–2015 PT@3 intake were used in the EE analyses,n= 265 (50%) in the FV arm andn= 269 (50%) in the TAU arm. Mean incremental cost per child in the FV arm was £68.37 (P= 0.382; 95% confidence interval [CI], –£18.04 to £143.82). Mean incremental QALY was −0.004 (P= 0.636; 95% CI, −0.016 to 0.007). The probability that the FV intervention was cost-effective at the UK £20,000 threshold was 11.3%.Conclusion:The results indicate that applying FV in nurseries in addition to TAU (all other components of Childsmile, apart from nursery FV) would not be deemed cost-effective given current UK thresholds. In view of previously proven clinical effectiveness and economic worthiness of the universal nursery toothbrushing component of Childsmile, continuation of the additional, targeted nursery FV component in its pre–COVID-19 form should be reviewed given its low probability of cost-effectiveness.Knowledge Transfer Statement:The results of this study can be used by child oral health policy makers and dental public health professionals. They can form part of the evidence to inform the Scottish, UK, and international guidance on community-based child oral health promotion programs.