Introduction: An ideal sealer produces a hermetic closure, does not cause tooth discoloration, is bacteriostatic, insoluble in tissue fluids and biocompatible, and has good adhesion and a long setting time. Until now, no sealer material has met all these criteria. This study analyzed the differences in sealer adaptation between epoxy resin calcium silicate-based sealers in the middle third of the root canal wall. Materials and Methods: Thirty-Two mandibular premolar teeth were prepared and divided into two groups (n = 16 each) according to the type of sealer used for obturation, Group 1 teeth were obturated with an epoxy resin-based sealer, and Group 2 teeth were obturated with a calcium silicate-based sealer. The teeth were cut vertically and prepared for scanning electron microscopy analysis. Sealer adaptation was scored and then analyzed statistically by a Chi-square test. Results: The adaptation scores were poor for 0 (0%) teeth, good for 13 (81.25%), and very good for 3 (18.75%) for the epoxy resin-based sealer and poor for 3 (18.75%) teeth, good for 5 (31.25%), and very good for 8 (50%) for the calcium silicate-based sealer. No statistically significant difference was detected between the adaptation of epoxy resin-based and calcium silicate-based sealers (P > 0.05). Overall, the particles appeared larger for epoxy resin than for calcium silicate. Discussion and Conclusion: No statistical difference was detected for sealer adaptation between epoxy resin-based and calcium silicate-based sealers in the middle third of the root canal wall. © 2023 Wolters Kluwer Medknow Publications. All rights reserved.