Aim: This in vitro study was conducted to evaluate and compare the fracture resistance of root filled with gutta percha and Epoxy Resin–based, Mineral Trioxide Aggregate–based, and Bioceramic root canal sealers. Methods: Sixty single-rooted extracted mandibular premolars were decoronated to obtain 14-mm root segments. All the root canals will be prepared using a rotary Pro-taper system up to size F3. All canals will be dried using paper points and divided into 5 groups based on root canal sealer used. Lateral compaction technique was used to obturate the sample. Group1: AH Plusjet, Group2: MTA Fillapex, Group3: EndoSequence BC Sealer, Group4: unprepared and unfilled. Group5: the teeth left unobturated. The roots within each group were embedded in acrylic molds and subjected to the fracture resistance test in which a compressive loading was applied until fracture. Data were statistically analyzed (One way ANOVA followed by pair-wise Tukey’s post-hoc tests were performed). Results: When comparing the fracture resistance of the tested groups, the results revealed that there was a statistical significant difference between the groups. It was found that Bio-ceramic group recorded statistically significant (P<0.05) highest fracture resistance mean value followed by unprepared and unfilled group then AH Plus jet group and MTA group. Conclusion: Bioceramic based sealer is a promising sealer in terms of increasing in vitro resistance to the fracture of endodontically treated roots.Clinical recommendations: Endo Sequence BC Sealer with gutta-percha is required to obturate weak and mutilated endodontically treated teeth, as it gave statistically the highest fracture resistance value comparable to that of non-instrumented teeth.