Context: The success of endodontic therapy depends on proper biomechanical preparation and obturation. Aim: To evaluate and compare the pushout bond strength (POBS) of MTA Fillapex (MF) and BioRoot RCS (BRCS) sealers in endodontically treated teeth with different irrigants-5.25% Sodium hypochlorite (NaOCl), 17% ethylenediaminetetraacetic acid (EDTA) and 0.2% Chitosan. Materials and Methods: 60 premolars were divided into three groups. Each group was then subdivided into A and B. The three groups were Group 1A: 17% EDTA + 5.25% NaOCl with MF sealer ( n = 10); Group 1B: 17% EDTA + 5.25% NaOCl with BRCS sealer ( n = 10); Group 2A: 0.2% Chitosan + 5.25% NaOCl with MF sealer ( n = 10); Group 2B: 0.2% Chitosan + 5.25%NaOCl with BRCS sealer ( n = 10); Group 3A: 5.25% NaOCl + MF sealer ( n = 10); and Group 3B: 5.25% NaOCl + BRCS sealer ( n = 10). After obturation, they were sectioned horizontally (1.5 mm thick). The POBS was studied using a universal testing machine (Autograph AG-1). The sample size was calculated using the statistical package G * Power (3.1.5). Results: It was found that the POBS of BRCS was higher when the root canal was irrigated with 0.2% Chitosan + 5.25% NaOCl. Thus, Group 2B showed significantly higher POBS than Group 2A. Conclusion: The irrigation regimen of Chitosan with NaOCl was found to have better debriding effect on the root canal. Of the two sealers, BRCS showed the higher bond strength values than MF.