Aim:The aim of this study was to assess the effect of three root canal irrigants on the apical sealing ability of three single-cone obturation systems. Materials and methods:One hundred maxillary central incisors were selected and their crowns were cut. The roots were divided into three experimental groups of 30 samples each, and one control group of 10 samples (5 positives and 5 negatives). Each experimental group was divided equally into three subgroups according to the obturation system. All root canals were instrumented using ProTaper Universal rotary system and irrigated with 3% sodium hypochlorite (Group 1), 2% chlorohexidine (Group 2), 3% hydrogen peroxide (Group 3). Finally, root canals were irrigated with 17% EDTA followed by distilled water, then obturated with a single-cone technique using gutta-percha/MTA Fillapex (Subgroup A), gutta-percha/ AH Plus (Subgroup B), and Resilon/Relseal SE (Subgroup C). The microleakage was assessed using linear dye penetration method and data were statistically analyzed.Results: Significant differences were found between all groups and subgroups (p < 0.005). When 3% of hydrogen peroxide was used, no leakage was observed with AH Plus sealer, and a high amount of leakage (5.82 ± 0.47 mm) was observed with Realseal SE. MTA Fillapex (0.49 ± 0.08 mm) and Realseal SE (1.11 ± 0.50 mm) showed the lowest amounts of leakage when 2% chlorohexidine and 3% sodium hypochlorite were used, respectively. Conclusion:The type of irrigating solution and obturation system could affect the apical leakage value when single-cone obturation technique was used. AH Plus/gutta-percha obturation system showed no apical leakage when root canals were irrigated with 3% hydrogen peroxide. The using of 2% chlorohexidine improved sealing ability of MTA Fillapex/gutta-percha. The apical sealing ability of Realseal SE/Resilon decreased when 3% hydrogen peroxide or 2% chlorhexidine was used.Clinical significance: Proper selection of irrigating solutions may positively influence the apical sealing ability of single-cone obturation systems.