Aim: This study is aimed to evaluate the impact of three irrigating solutions on the apical sealing ability of three endodontic sealers. Materials and Methods: One hundred maxillary central incisors were decoronated, and their roots were assigned into three experimental groups (n = 30 each) according to the nature of the irrigating solution and two control groups (n = 5 each). Each experimental group was divided equally into three subgroups (n = 10 each) according to the type of root canal sealer. All root canals were instrumented using ProTaper Universal rotary system and irrigated with 3% sodium hypochlorite (NaOCl/Group 1), 3% hydrogen peroxide (H2O2/Group 2), and 2% chlorhexidine gluconate (CHX/Group 3). The final irrigating solutions for all groups were 17% ethylenediaminetetraacetic acid (EDTA) and distilled water. The continuous-wave technique was used to fill the prepared canals with the following materials: MTA-Fillapex/Gutta-percha (Subgroup A), AH Plus/Gutta-percha (Subgroup B), and Realseal SE/Realseal (Subgroup C). The microleakage was assessed after 72 hours using the linear dye penetration method. The results were statistically analyzed with one-way analysis of variance. Results: Significant differences were found only between the experimental groups (P < 0.05). All root canal sealers after irrigation with 3% H2O2showed the lowest amount of leakage. The highest apical leakage was observed when 3% NaOCl and 2% CHX were used. Conclusions: The type of irrigating solution could affect the apical sealing ability of experimental sealers used with the continuous-wave obturation technique. Root canal irrigation with 3% H2O2+17% EDTA increased the apical sealing ability of all root canal sealers. Root canal irrigation with 3% NaOCl or 2% CHX +17% EDTA decreased the apical sealing ability of all root canal sealers. © 2020 Wolters Kluwer Medknow Publications. All rights reserved.