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 concerningthe 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