Introduction: This study assessed the fracture resistance (FR) of teeth with simulated perforating internal resorption cavities repaired with different calcium silicate based cements (CSCs) and backfilling materials. Methods: Ninety-six mandibular premolar teeth were used. Twelve of the teeth were assigned as negative control group. Remaining roots were instrumented with rotary files, and standardized internal resorption cavities were prepared on the middle half of roots with burs. Twelve of the samples were not further interfered and were assigned as a positive control group. The apical 4 mm of the remaining 72 root canals was obturated with single-cone technique and divided into 6 groups according to CSCs used for repairing of cavities and backfilling materials as follows: MTA + MTA, MTA + gutta-percha/sealer, Biodentine + Biodentine, Biodentine + gutta-percha/sealer, MTA Plus + MTA Plus, and MTA Plus + gutta-percha/sealer. Specimens were embedded in acrylic resin and then subjected to fracture testing. The forces when the fracture occurred were analyzed with analysis of variance and Bonferroni tests at P = .05. Results: No significant difference was found among CSCs irrespective of backfilling materials (P > .05). Groups MTA + gutta-percha/sealer, Biodentine + gutta-percha/sealer, and MTA Plus + gutta-percha/sealer showed significantly lower FR compared with groups MTA + MTA, Biodentine + Biodentine, and MTA Plus + MTA Plus, respectively (P < .05). The highest FR was observed in group Biodentine + Biodentine, and the lowest was in group MTA Plus + gutta-percha/sealer. FR of positive control group was statistically lower than groups completely filled with CSCs (P < .05), whereas FR of negative control group was statistically higher than the groups combined with gutta-percha and sealer (P < .05). Conclusions: The backfilling with CSCs may be a preferable material rather than gutta-percha/sealer combination for the roots with perforated internal resorptions.