Background <p>Limited clinical evidence is currently available on the retention rates of the silver-nanoparticles filled pit and fissure sealant in permanent molars.</p> Aim <p>To compare the retention rates of a resin-based sealant with silver-nanoparticles with that of a conventional resin-based sealant on permanent molars in children.</p> Methods <p>A split-mouth design was used. Six to fourteen years old children (<i>n</i> = 150) reporting to a tertiary care hospital were recruited. A total of 264 pairs of permanent molars were subjected to one of the two interventions-A—Resin-based sealant without silver-nanoparticles (Helioseal F plus sealant); B—resin-based sealant with silver-nanoparticles (e-pit and fissure sealant). Sealants were applied using a standardized technique by a single-blinded operator. Primary outcome was the retention of the sealants and secondary outcomes were the presence or absence of caries, surface roughness, marginal integrity and discoloration of the sealant material. Follow-up evaluations were conducted at 6- and 12-months by two blinded evaluators. Data were analysed using the Chi-square test and <i>p</i>-value less than 0.05 was considered to be significant.</p> Results <p>At 12&#xa0;months, 224 pairs of permanent molars were available for analysis. The test sealant, e-Pit and fissure sealant performed better in terms of retention (68.3% of sealants with silver-nanoparticles retained as compared to 53.6% of resin-based sealants Helioseal F plus; <i>p</i> = 0.001), surface roughness, marginal integrity and sealant discoloration (<i>p</i> &lt; 0.05). The occurrence of caries did not differ significantly between the two groups (<i>p</i> = 0.391).</p> Conclusion <p>The study concluded that e-pit and fissure sealant with silver-nanoparticles had a better retention rate as compared to the Helioseal F plus sealant but caries occurrence was not different between the two groups.</p> Trial registration number <p>CTRI/2022/05/042622.</p>