This study compared the efficacy of HyFlex NT (HF; Coltene, New York, NY) and Mani GPR (MN; Mani Inc, Tokyo, Japan) systems followed by a supplementary approach with passive ultrasonic irrigation (PUI) in removing the filling material from curved root canals during retreatment. The mesial canals from 20 extracted mandibular molars with Vertucci type IV configuration were instrumented and obturated (N = 40). Each mesial canal was retreated using either HF or MN instruments, alternating the system used per canal from root to root. The final preparation size was 40/0.04 for both systems. The volume of canal filling material was assessed by means of micro–computed tomographic (micro-CT) imaging before and after retreatment, and the working time was recorded. Canals still showing remnants of filling material were subjected to a supplementary approach with PUI, and another micro-CT scan was taken. The percentage of filling material removed with MN instruments and HF was similar (95.5% and 92.7%, respectively) (P > .05). MN required significantly less time to remove the filling material (P < .05). The supplementary approach with PUI significantly enhanced the removal of filling material (P < .05). Both systems were equally effective in removing the root canal filling during retreatment. MN was faster than HF. The supplementary approach with PUI significantly improved filling material removal. •The amount of filling material removed with Mani GPR and HyFlex NT was similar.•Mani GPR required less time to remove the filling material than HyFlex NT.•Passive ultrasonic irrigation significantly enhanced the removal of filling material.