Objectives: The purpose of the study was to evaluate the effect of glass ionomer fissure sealant on the prevention of occlusal caries in erupting permanent second molars. Methods: The sample included all grade 3 and 4 children (437), with second molars in the process of eruption, selected from schools in the Robertson area of the Western Cape Province of South Africa. These children (437), meeting the inclusion criteria, varied between 9–14 years of age and were subsequently randomly divided into a test and control group. The caries experience (DMFS) of both the test and control group was determined at baseline. The test group then received glass ionomer fissure sealant (Fuji III LC, GC Corporation, Japan) on the erupting second molars. Three follow-up examinations were conducted annually assessing occlusal caries experience on the second molars, overall caries experience (DMFS) as well as clinical status of the fissure sealants. Results: After three years the overall drop out rate was 28% representing 27% and 28% in the test and control groups respectively. The average age for the total sample was 10.7 (±1.26) years and did not differ between the test and control groups. Complete fissure sealant retention decreased from 11% after one year to 1% after three years. Partial or no fissure sealant retention with no caries varied between 88% and 81%, whereas partial or no retention with caries development varied between 3% and 11% for the study period. After three years 82% of occlusal surfaces in the test group were caries free compared to 26% in the control group. Although the caries experience of the two groups were similar at baseline, the test group had on average two fewer carious surfaces at the third follow-up. Conclusion: Despite poor retention the glass ionomer fissure sealant afforded significant occlusal protection in erupting second molars.