Since 2008, FRAMM has been a guideline for caries prevention for all 3- to 15-year-olds in the Västra Götaland Region in Sweden and a predominant part is school-based fluoride varnish applications for all 12- to 15-year-olds. The aims were to evaluate dental health-economic data among 12- to 15-year-olds, based on the approximal caries prevalence at the age of 12, and to evaluate cost-effectiveness. Caries data for 13,490 adolescents born in 1993 who did not take part and 11,321 adolescents born in 1998 who followed this guideline were extracted from dental records. Those with no dentin and/or enamel caries lesions and/or fillings on the approximal surfaces were pooled into the “low” subgroup, those with 1-3 into the “moderate” subgroup and those with ?4 into the “high” subgroup. The results revealed that the low subgroup had a low approximal caries increment compared with the moderate and high subgroups during the 4-year study period. In all groups, there were statistically significant differences between those who took part in the guideline and those who did not. The analysis of cost-effectiveness revealed the lowest incremental cost-effectiveness ratio (ICER) for the high subgroup for decayed and/or filled approximal surfaces (DFSa) and approximal enamel lesions together and the highest ICER for the low subgroup for DFSa alone. To conclude, the FRAMM Guideline reduced the caries increment for adolescents with low, moderate and high approximal caries prevalence. The subgroup with the most favourable cost-effectiveness comprised those with a high caries prevalence at the age of 12.