To evaluate the efficiency of debris removal from the mesial root canals and isthmus of mesial roots of mandibular molars after final irrigant agitation with XP-endo Shaper, EndoVac (EV), plastic finishing file, and conventional needle irrigation. Forty extracted human mandibular first molar teeth with the isthmus between the mesial roots were selected, access cavities were prepared and distal roots were decoronated. All the mesial root specimens were mounted in acrylic, sectioned at the coronal, middle, and apical thirds, along with the resin block, and examined for debris in the canals and isthmus before the start of the procedure using a stereomicroscope and were mounted back in a custom-made jig. After determination of the working length, they were allocated to the following four different irrigant activation groups (n = 10): Group I-XP-endo Finisher; group II-EndoVac; group III-plastic finishing file; and group IV-standard needle irrigation. After biomechanical preparation (BMP) till F3, final agitation was done for debris removal with the respective agitating devices, and all the samples were examined under a stereomicroscope for the amount of debris in the canal after final agitation. Of all the irrigation devices used, the XP-endo Finisher and EV showed more debris removal when compared to other groups (p < 0.05). The plastic finishing file in continuous rotation was more efficient in cleaning debris compared with conventional needle irrigation (p < 0.05). The XP-endo Finisher and EV showed a significant difference in cleaning efficacy than the plastic finishing files. So, these can be used as adjunctive for agitating the final irrigant. The irrigant agitation devices promote the penetration of irrigants into the intricate root canal anatomy and increase their antibacterial and tissue-dissolving effectiveness thereby improving the success rate and treatment outcome.