The aim of this study was to evaluate the efficacy of activated irrigants (EDTA e NaOCL) during the cleansing of root walls, of the smear layer, of the debris, and gutta-percha after the preparation of the restorative space. Twenty single and multi-rooted (n = 20) have been collected. All samples were prepared by the same operator, using Nickel-titanium rotating instruments (Mtwo) through the Simultaneous Shaping Technique. The continuous-wave of condensation technique of obturation was used. To all specimens, the restorative space has been made, leaving 5 mm of apical gutta-percha, and postoperative periapical X-rays were performed. The samples were randomly divided into two groups: Group (A): cleansing of the root walls with ultrasonic activation of the irrigants (NEWTRON P5 XS; Satelec Acteon); Group (B): radicular walls wash without ultrasonic activation of endodontic irrigants (NaOCl 5.25% and EDTA 17%). Both dental sample groups were cut longitudinally with a low-speed saw (Isomet); the samples were observed by using a scanning electron microscope (Jeol, Jsm-6060LV) in order to evaluate: (1) the amount of debris/smear layer; (2) the mount of obstruction of dentinal tubules found in the two groups; and (3) evaluation of the presence of gutta-percha. Then, the other five samples each group (with and without ultrasonic activation) were prepared following the same protocol. Then, a universal bonding system (G-Praemio Bond, GC) and a layer of a flowable resin composite (Gaenial Flow, GC) were light-cured and used on top of the prepared root canal walls. The samples were cut in two pieces along the long axis of the root. Then, half sample teeth were kept in an acidic solution (37% HCl) for 48 h in order to completely dissolve dental structures and to have a direct view of resin tags formation under SEM. The other half was prepared to observe the adhesive interface under SEM. The amount of debris was not satisfactory in 9 out of 10 cases in Group B, while in Group A, which has been treated with ultrasounds, the result was either good or great in most of the samples. For the sample group treated with ultrasound, the tubules were evaluated as perfectly clean in 9 out of 10 cases, instead, the results are unsatisfactory for 9 out of 10 cases of group B not treated with ultrasound. Differences between Group A and B were statistically significant. With respect to the presence of debris and tubules obstruction treatment with ultrasonic activation, it offers with no doubt better results. When ultrasonic activation is used in combination with endodontic irrigants, a clean dentin substrate is be obtained for the adhesion of restorative materials, but in order to confirm the findings of this study, further in vivo trials are needed.