Aim: The study was conducted to evaluate the effect of ultrasonic irrigation activation on the depth of penetration of bioceramic sealer (CeraSeal) and Epoxy resin sealer (Adseal) into the dentinal tubules with cold lateral compaction obturation technique. Materials and Methods: 56 extracted upper central incisors were divided randomly into four experimental groups (each group, n = 14) based on sealer type and irrigation method. Obturation of teeth was performed using lateral compaction technique. Scanning electron microscope (SEM) was used to evaluate sealer penetration at 1600x magnification. Results: CeraSeal has significantly higher tubular penetration with ultrasonic activation in all sections. There was significant difference between all sections among each group as coronal was significantly the highest while apical was significantly the lowest. Conclusion: According to the limitations of the present study, irrigation activation is an essential step in canal preparation for better smear layer removal that gives deeper sealer penetration inside the dentinal tubules leading to a higher sealing ability of obturation. Bioceramic sealers have higher sealing ability than Epoxy resin sealers.