The primary objective of this study was to evaluate the effects of sealants in preventing pit and fissure caries in primary molars. The secondary objective was to assess the sealant retention during a 2-yr study period. A 2-yr split-mouth randomized clinical trial including 90 3-7-yr-old children was conducted in the paediatric dental department of Montpellier hospital. The dentition of each included patient was divided into an experimental side and a control side, with annual follow-up visits. Caries increments, measured as the number of new occlusal cavitated lesions, were not different between the sealed (mean 0.23) and the control primary molars (mean 0.29). A multiple mixed-effects logistic regression showed that male gender, moderate/high caries risk, and a higher oral hygiene index score, had a statistically significant effect resulting in higher caries increments in the primary molars, than did female gender, low caries risk, and lower oral hygiene index scores. Sealing showed no statistically significant influence on the development of new caries lesions. After 2 yr, the percentages of partially or totally lost sealants were 22.7% and 32.0%, respectively. In this sample of children, the caries increment was not significantly different between the sealed and the unsealed molars. At the end of this 2-yr study, more than half of the sealants were totally or partially lost, which could explain the low sealant effectiveness.