Objective The aim of this study was to evaluate the efficacy of different irrigation protocols in removing two tricalcium silicate-based sealers from simulated root canal irregularities and root canal walls. Material and methods Root canals of 140 single-rooted teeth were instrumented. In one-half of each root, an apical groove was created. The samples were divided into two main groups (n = 70) based on the sealer used. In group 1, the grooves were filled with MTA Fillapex; in group 2, BioRoot RCS. The reassembled root halves were divided into six experimental and one control groups: 2.5% NaOCl-17% EDTA (Passive ultrasonic irrigation [PUI]), 5% NaOCl/9% DualRinse HEDP (PUI), 2.5% NaOCl-7% Maleic acid (PUI), 2.5% NaOCl-17% EDTA (Er:YAG laser activated irrigation [LAI]), 2.5% NaOCl/9% DualRinse HEDP (LAI), 2.5% NaOCl-7% Maleic acid (LAI), Distilled water (Control). Specimens were scored using SEM. The data were analysed using Kruskal-Wallis and Mann Whitney U tests. Results Maleic acid and DualRinse HEDP removed higher amounts of MTA Fillapex from the grooves compared to EDTA, when used with both activation methods (p < .001). Conclusions Ultrasonically activated maleic acid or DualRinse HEDP can be an effective irrigation regimen in removing tricalcium silicate-based sealers.