OBJECTIVE To evaluate the effectiveness of resin-based sealants and glass ionomer sealants on caries prevention in the first permanent molars. METHODS A randomized controlled, examiner-blinded, 2-year clinical trial with parallel groups was conducted. A total of 419 children (664 first molars) who had at least one sound first permanent molar with deep fissures or fissures with signs of non-cavitated lesions were recruited. They were randomly allocated into three groups.Helioseal F, a light-cured resin-based sealants was used in group R (136 children with 219 first molars). FUJI VII, a light-cured glass ionomer sealants was used in group G (130 children with 218 first molars) and group N (153 children with 227 first molars) was blank control.Follow-up examinations were conducted at 6, 12, and 24 month after sealing to examine the sealants retention and caries incidence. Chi-square test was used to compare the differences of caries incidence among the 3 groups.Generalized estimating equations (GEE) was used to analyze the effective factors of caries incidence. RESULTS During the 2-year follow-up period, 3.0% (6/197) of the teeth in group R, 6.7% (13/193) of the teeth in group G, and 14.7% (29/197) of the teeth in group N were diagnosed as having developed a cavitated lesion. The difference in the incidence of caries among the three groups was significant(P < 0.05). No significant difference in caries incidence was found between group R and group G (P > 0.05). The tooth-level preventive fractions were 79.6% for resin-based sealants and 54.4% for glass ionomer sealants, respectively. CONCLUSIONS Both resin-based sealants and glass ionomer sealants can effectively prevent the incidence of caries in the first permanent molars. The two sealants have similar caries prevention effect.