Aim: To evaluate the effect of 17% ethylenediaminetetraacetic acid (EDTA) and 7% maleic acid (MA) irrigation on microleakage of mineral trioxide aggregate (MTA) and Biodentine® (BD) when used as a root-end filling material. Materials and Methods: Sixty human anterior teeth were decoronated and subjected to root canal instrumentation. 3 mm of apical root portion was resected, and root-end cavities were prepared using ultrasonic tips. Teeth were then randomly divided into two groups (n = 30). Group 1 - root end cavity to be filled with MTA; Group 2 - root end cavity to be filled with BD. Each group was further divided into three subgroups A, B, and C based on irrigation regimen. Group A - 17% EDTA; Group B - 7% MA; Group C - 0.9% saline. About 5 mL of all irrigating solutions were used for 1 min. After final irrigation, root-end cavities were filled with respective root end filling material. Specimens were then subjected to microleakage analysis at 24 h, 7 days and 14 days using glucose filtration technique. For smear layer evaluation, six central incisors were subjected to root canal instrumentation and irrigation with 7% MA and 17% EDTA. Then, these samples were analyzed under the standard error of the mean data was analyzed using one-way ANOVA, Bonferroni test, Mann–Whitney U-test and Kruskal–Wallis test. Results: Saline group demonstrated significant higher leakage than that of 17% EDTA and 7% MA in both MTA and BD groups. However, there was no significant difference between 17% EDTA and 7% MA group when MTA was used as root-end filling material. In BD group, 17% EDTA showed more leakage than 7% MA. 7% MA was able to remove the smear layer better than 17% EDTA. Conclusion: MTA had a better sealing ability as compared to that of BD when root-end cavities were irrigated with 7% MA.