Purpose: To evaluate and compare the long-term outcome of a population-based and a risk-based strategy of applying fissure sealants in newly erupted first permanent molars. Design and Setting: Retrospective cohort study in primary dental care. Materials and Methods: Four hundred and ninety-six subjects from two cohorts were included. In group P (n = 236), routine applications of fissure sealants were conducted while sealants were placed on the basis of subjective criteria in Group R (n = 260). Data of applications, maintenance, decay, restorations, extractions, and cumulative time of applications from six to 19 years were extracted from the dental records and bite-wing radiographs by two of the authors simultaneously. The main outcome measures were the total caries prevalence at the age of 19 years as well as the fate of each sealed and non-sealed occlusal surface. Results: In group P, 87.7% of all first permanent molars were sealed compared with 20.2% in group R. There was no statistically significant difference concerning the total DFT at 19 years of age between the groups (mean 3.5 ± 3.8 vs. 3.7 ± 3.4). Considering the occlusal surfaces of the first permanent molars only, a statistically significant treatment effect was demonstrated in group P with an odds ratio of 4.6 (95% CI: 3.0 - 6.7; p 0.05). The absolute risk reduction was 36.3% and the number needed to treat was 2.8. In Group R, no statistically significant treatment effect was disclosed (OR = 1.3; 95% CI: 0.9 - 1.7; risk reduction 5.5%). Conclusion: This 13-year follow-up showed that population-based applications of fissure sealants in first permanent molars shortly after eruption showed a statistically significant treatment effect on the occlusal surfaces at the age of 19 years, which was in contrast to findings from a cohort in which sealants were applied on the basis of an individual risk-based strategy. There were, however, no significant differences concerning the total caries experience between the two cohorts. Keywords: caries prevention, first permanent molars, fissure sealants, preventive strategies