Background: This study compared conventional-resin-sealant versus nanofilled-sealant retention at different intervals. Methods: A double-blinded split-mouth randomized control trial was performed on sixty-two children aged from six to nine years. Participants with one pair of contralateral permanent first molars with deep fissures or noncavitated carious lesions were randomly selected for sealant application. Conventional resin sealant was applied on one molar and nanofilled sealant on the contralateral molar. Evaluations were performed at one, three, six, twelve and eighteen months to check for retention. The chi-squared test, McNemar test, Wilcoxon signed-rank test and Friedman test were used for statistical analysis. Results: Conventional resin sealant showed complete retention in 91.4%, 86.2%, 74.1%, 62.1% and 55.2% of the teeth, and nanofilled sealant showed complete retention in 89.7%, 81%, 77.6%, 69% and 67.2% of the teeth, at the end of 1 month, 3 months, 6 months, 12 months and 18 months evaluation, respectively. Each sealant exhibited a statistically significant change (p < 0.05) in the retention rate during the evaluation period. However, when both the sealants were compared with each other, there was no statistically significant difference in any phase. At the end of 18 months, caries development was observed in 13.8% of the teeth sealed with conventional sealant, and in 10.3% of the teeth sealed with nanofilled sealant. Conclusion: At eighteen months, the nanofilled resin sealant exhibited complete retention in 12% more teeth than the conventional sealant. However, the difference was not statistically significant. The nanofilled resin sealant yielded an acceptable performance in sealing the occlusal pits and fissures of mandibular permanent first molars, compared to conventional pit-and-fissure sealants.