Objective To compare preventive effect on dental caries of two frequencies of fluoridated varnish (FV) applications and a group given brushing instructions and using fluoridated toothpaste. Materials and Methods Follow-up study of 203 children attending an elementary school in the municipality of Tláhuac, Mexico City. The children were followed for 22 months. The students were randomly assigned to one of the following groups: 1) brushing instructions with fluoridated toothpaste, 2) FV every six months, 3) three FV applications per week per year. The FV contained fluorosilane (1000 ppm F) and NaF dentifrice (1450 ppm F). The DMFT-caries index and the presence of white spots were recorded (ICDAS, International Caries Detection and Assessment System). Results At baseline, the mean age of the children was 9.3 (SD 0.76) years, white lesions 0.63 (SD 1.48) and DMFT =0.70 (SD 1.11). Averages of the initial and final DMFT scores in the three groups were 0.67 and 1.17 for the toothpaste group, 0.77 and 1.46 for FV twice a year group, and 0.67 y 1.03 for the three-applications-FV group. According to the results of the GEE (Generalized-Estimating Equations) model, there were no significant differences in the rate of white lesions or the increase of the DMFT index. The results for the DMFT were: for bi-annual applications of FV, RR=1.24 (p=0.178) and for the three consecutive applications of FV, RR=0.83, (p=0.298) in comparison with the brushing-instructions group using fluoridated toothpaste, among the three treatment groups, controlling for age, sex, and initial-caries index in primary teeth and brushing frequency. Conclusions Schoolchildren showed a low incidence of caries using any of the three preventive regimens applied.