Considering previous literature, it has been thought that different file motions and root canal sealers used during retreatment may affect the fracture resistance of the endodontically retreated teeth. This study aims to compare the fracture resistance values of retreated teeth with two different file systems and re-obturated with gutta-percha and different sealers. Sixty extracted lower premolars were prepared up to ProTaper Universal-F4 (PTU) and filled with resin-based sealer (RBS) and gutta-percha. Thirty teeth were re-prepared with PTU retreatment files and ProTaper Universal-F5. The remaining 30 teeth were re-prepared with Reciproc-50 files. Fifteen teeth from each group were filled with RBS, or calcium
silicate-based root canal sealer (CSBS), and F5 or R50 gutta-percha. After the setting of filling materials, a fracture test was performed. Data were analyzed with a two-way ANOVA and chi-square test (p < 0.05). There was no significant difference among the groups (p > 0.05). The lowest mean was observed in the PTU-CSBS group (277.80 ± 105.47 N), and the highest mean was observed in the PTU-RBS group (335.05 ± 121.05 N). A buccolingual irreparable fracture was common in all groups (p < 0.05). Specimens retreated either with rotational or reciprocating files could be re-obturated with a combination of guttapercha and RBS or CSBS.