Objective: This study aims to evaluate the influence of Nd:YAG and diode laser irradiation on apical sealing when applied before root canal filling done with two different resin-based cements (AH Plus and EndoREZ). Background Data: Lasers have been widely used in endodontics. The morphologic changes in dentin walls caused by Nd:YAG and diode laser irradiation could improve sealing ability of endodontic cements. Methods: Eighty canine teeth were analyzed by apical leakage of methylene blue dye and by scanning electron microscope (SEM) images of the filling's adaptation to the apical third dentin walls. The laser irradiation parameters for the Nd:YAG laser were 100 mJ, 15 Hz, and 1.5 W, and for the diode laser was 2.5 W (continuous mode). Results: The apical leakage results showed statistically significant differences at the 5% level of significance (Tukey's test, p < 0.05) among the different root canal wall treatments, independently of the root canal filling cement used. The cements also showed significant differences between them on the lased groups. The SEM analysis revealed better filling adaptation for AH Plus and the Nd:YAG laser group, confirming the microleakage results. Conclusion: We concluded that the combination of the Nd:YAG laser and AH Plus showed the best results.