This study compared the effect of four calcium silicate-based sealers and sealer extrusion on postoperative pain (POP).A total of 42 patients, having their first or second mandibular molars without apical periodontitis necessitating vital pulp therapy, were included in the study. The shaping protocol was done using R-motion® (FKG, Switzerland). The irrigation protocol was similar for all the groups. The sample was randomly divided into 4 groups that were obturated as follows: G1 with TotalFill® BC sealer (FKG, Switzerland), G2 with Bio-C® sealer (Angelus, Brazil), G3 with AH Plus BC sealer® (Dentsply, Sirona, USA), and G4 with K-sealer® (Rekita, Lebanon). The patients were followed during the 24, 48, and 72 h and 7 days postoperatively using the Visual Analog Scale (VAS) pain scoring and were recalled for percussion test at day 7. Statistical analysis was performed using the IBM SPSS Statistics (version 25) software.A significant reduction was found between preoperative VAS score and the VAS score over time. As per the type of sealer, a significant difference in VAS score was found at 24 h for Bio-C, at 72 h for AHPBC, and at 7 days for K-sealer and TFBC. A significant correlation was observed between the percussion test and the type of sealer, with the best improvement for TFBC. No statistically significant differences were found between the extrusion status and the percussion diagnostic.Despite the type of the sealer used, pain will decrease within time. Bio-C sealer was the fastest sealer in reducing POP, followed by AHPBC, K-sealer, and TFBC. There is a statistical difference in the percussion test between preoperatively and after 7 days with all the sealers, but the best improvement was visible with TFBC. Unintentional sealer extrusion did not affect the POP.