Aim and Objectives:The aim of the study was to compare and evaluate the push-out bond strength (POBS) of epoxy resin-based and calcium silicate-based sealers with and without incorporating chitosan nanoparticles (CSNPs).Methodology:Eighty human mandibular premolars with a single canal were taken. A standard root length of 15 mm was established. Canals were instrumented with Neoendo files up to size 30, 4% and were irrigated with 5 ml of 2.5% NaOCl, and 5 ml of ethylenediaminetetraacetic acid 17%. Then, samples were obturated using the size 30, 4% gutta-percha, single-cone technique using respective sealers. For POBS, it was grouped as Group 1 Adseal, Group 2 CeraSeal, Group 3 Adseal + 2% wt/vol CSNP, and Group 4 CeraSeal + 2% wt/vol CSNP. Samples embedded in acrylic resin were sectioned transversely at 11 and 7 mm from the apex. Dislodgment resistance was calculated using a universal testing machine. The data were analyzed using a one-way ANOVA test, followed by Tukey’s post hoc analysis. The level of significance (P value) was set at P < 0.05.Results:At 7 mm from the apex, Group 4 (CeraSeal + 2% wt/vol CSNP) demonstrated significantly higher mean POBS. However, no significant difference was observed between Groups 1 (Adseal), Group 2 (CeraSeal), and Group 3 (Adseal + 2% wt/vol CSNP). At 11 mm from the apex, Group 2 (CeraSeal) and Group 4 (CeraSeal + 2% wt/vol CSNP) demonstrated significantly higher mean POBS. On comparison between POBS at 7 mm and 11 mm from the apex, the mean POBS at the 11 mm region from the apex was significantly higher in all study groups, which was statistically significant.Conclusion:Within the limitations of the study, it has been concluded that Group 4 (CeraSeal + 2% wt/vol CSNP) has better bond strength compared to the other groups.