Aim: The purpose of the present study was to compare the efficacy of three different file systems in removing gutta-percha during endodontic retreatment with or without solvents. Materials and methods: The current study used 120 freshly extracted, single-rooted human mandibular premolars extracted for orthodontic procedures. The canal was prepared utilizing the step-back technique and obturation was done. The samples were allocated into three experimental groups at random, group I: Hedstrom Files, group II: D-RaCe rotary system, and group III: Mtwo retreatment files system. The three groups were again split into two subgroups of 20 samples each, i.e., with solvent and without solvent. Then, a stereomicroscope with a magnification of × 20 was used to examine the samples. The amount of GP and sealer left was measured in three sections: At apical third (1 mm above the apex), middle third (8 mm from the apex), and coronal third (2 mm below the cementoenamel junction). The obtained data were analyzed using parametric Analysis of Variance (ANOVA). p-values less than 0.05 were considered significant. Results: The overall least debris on the dentinal surface was found in the middle third with/without solvent. The D-RaCe rotary system was 1.24 ± 0.11 and 1.44 ± 0.14, Mtwo retreatment files system was 1.38 ± 0.17 and 1.72 ± 0.09 and Hedstrom files was 2.08 ± 0.21 and 2.18 ± 0.16 respectively and A significant difference was found between the three different file system groups (p < 0.001). Conclusion: The current study concluded that, when combined with a solvent, the D-RaCe rotary retreatment system is more effective than the Mtwo rotary retreatment system and Hedstrom Files in removing gutta-percha and sealant from root canal walls. Clinical significance: When it comes to treating chronic infections, non-surgical retreatment is a more cautious method than periapical surgery. Retreatment should be performed efficiently and with appropriate instruments to ensure effective treatment.