Abstract Introduction This study compared the efficacy of a reciprocating single-instrument system and a rotary multi-instrument system followed by a supplementary approach with a finishing instrument in removing the filling material from curved canals during retreatment. Methods Forty mesial canals from extracted mandibular molars were instrumented and filled. Then, each mesial canal was retreated by using either Reciproc (VDW, Munich, Germany) or Mtwo (VDW) instruments, alternating the technique used per canal from root to root. The working time was recorded, and the percentage of removed filling volume was assessed by means of micro–computed tomography imaging before and after retreatment. Canals still showing filling material remnants were subjected to an adjunctive approach with the XP-Endo Finisher (FKG Dentaire, La Chaux-de-Fonds, Switzerland), and another microCT scan was taken. Data were statistically analyzed with a significance level of 5%. Results The percentage of filling material removed with Mtwo instruments (96%) was significantly higher than Reciproc (89%) ( P  < .05), both used up to a final instrument size of 40. Mtwo required less time to remove the filling material than Reciproc ( P  < .05). Intragroup analysis in the Reciproc group showed that the R40 instrument removed significantly more filling material than R25 ( P  < .05). The supplementary approach with the XP-Endo Finisher was effective in significantly enhancing the removal of filling material ( P  < .05). Conclusions The rotary multiple-instrument system was more effective and faster than the reciprocating single-instrument approach in removing previous root canal fillings. As for the Reciproc group, it was observed that the larger instrument promoted significantly better results. The adjunctive finishing instrument XP-Endo Finisher significantly improved filling material removal.