Objectives: This study evaluated the impact of different methods of irrigant agitation on smear layer removal in the apical third of curved mesial canals of 3 dimensionally (D) printed mandibular molars. Materials and Methods: Sixty 3D-printed mandibular second molars were used, presenting a 70° curvature and a Vertucci type II configuration in the mesial root. A round cavity was cut 2 mm from the apex using a trephine of 2 mm in diameter, 60 bovine dentin disks were made, and a smear layer was formed. The dentin disks had the adaptation checked in the apical third of the teeth with wax. The dentin disks were evaluated in environmental scanning electron microscope before and after the following irrigant agitation methods:G1(PIK Ultrasonic Tip), G2 (Passive Ultrasonic Irrigation with Irrisonic– PUI), G3 (Easy Clean), G4 (HBW Ultrasonic Tip), G5 (Ultramint X Ultrasonic tip), and G6 (conventional irrigation-CI) (n = 10). All groups were irrigated with 2.5% sodium hypochlorite and 17% ethylenediaminetetraacetic acid. Results: All dentin disks were 100% covered by the smear layer before treatment, and all groups significantly reduced the percentage of the smear layer after treatment. After the irrigation protocols, the Ultra-X group showed the lowest coverage percentage, statistically differing from the conventional, PIK, and HBW groups (p < 0.05). There was no significant difference among Ultramint X, PUI-Irrisonic, and Easy Clean (p > 0.05). None of the agitation methods could remove the smear layer altogether. Conclusions Ultramint X resulted in the most significant number of completely clean specimens.