This study aimed to compare the effects of ethylenediaminetetraacetic acid (EDTA) and maleic acid (MA) on the sealing ability of various root canal sealers. Eighty root canals were instrumented and irrigated with either EDTA or MA. They were divided into eight experimental groups and obturated as follows: Group 1: MA + Hybrid Root SEAL/gutta-percha. Group 2: EDTA + Hybrid Root SEAL/gutta-percha. Group 3: MA + iRoot SP/gutta-percha. Group 4: EDTA + iRoot SP/gutta-percha. Group 5: MA + EndoREZ/EndoREZ points. Group 6: EDTA + EndoREZ/EndoREZ points. Group 7: MA + AH Plus/gutta-percha. Group 8: EDTA + AH Plus/gutta-percha. Another ten roots were used as negative and positive controls. The microleakage of each sample was measured at 2-min intervals for 8 min using the fluid filtration method. Data were statistically analyzed with one-way ANOVA, post-hoc Tukey, and paired-samples t tests. The minimum microleakage values were obtained from the teeth obturated with AH Plus and EndoREZ selaers (p < 0.001). The samples with Hybrid Root SEAL showed the maximum leakage (p < 0.001). There were significant differences between the groups irrigated with MA or EDTA in terms of microleakage (p < 0.05). Use of MA resulted in higher microleakage values compared with those using EDTA. The type of final irrigation solution seems to influence the postobturation apical seal. Use of AH Plus and EndoREZ sealers showed better sealing ability compared with IRoot SP and Hybrid Root SEAL.