The effectiveness of fissure sealants in caries prevention depends on their long-term retention and ability to stop caries progression. This randomized controlled clinical trial compared the retention rate and cariostatic properties of a contemporary glass-ionomer-based sealant (GIS) versus a resin-based sealant (RS) placed on fully erupted permanent molars in a split-mouth design. The sealants were placed on fully erupted permanent teeth (8‒12 years of age) in 45 children. The evaluation was conducted after one week and three and six months. There was a statistically significant difference in the retention rate and caries transition between the two groups over a six-month clinical evaluation period. The resin-based sealant group showed a better retention rate than the GIS group (75.56% and 48.88%, respectively). The resin-based sealant was superior to GIS in preventing caries progression. Resin-based fissure sealant with fluoride releasing properties might be preferable in preventing caries progression of incipient non-cavitated carious lesions in fully-erupted teeth.© 2020 Jaafar et al.