Aim: The aim of this study is to compare the effect of different root canal sealers on the fracture resistance of endodontically treated teeth using AH Plus, GuttaFlow 2, MTA-Fillapex, and TotalFill® BC™ sealers. Materials and methods: Sixty single-rooted mandibular premolar teeth were used in the study. After the decoronation of the crowns of the teeth, we got a 13 mm root length. All samples instrumented using ProTaper Next system reaching file size ×4 as the final master apical file. Gutta-percha (GP) with single cone as obturation technique was carried out to all experimental teeth. Then, the teeth was divided into five groups (n = 12) based on the type of sealer to be used. Group I: AH Plus sealer + GP, Group II: GuttaFlow 2 sealer + GP, Group III: MTA-Fillapex sealer + GP, Group IV: TotalFill BC sealer + GP, and Group V: control (instrumented but unobturated teeth). Embedding all teeth in acrylic resin blocks was carried out and fracture force was measured using a universal testing machine (Instron Corp., Canton, MA, USA) by using metal-like spreader tip on 0.5 mm/m speed. Then, the data were statistically evaluated using one-way analysis of variance (ANOVA) and post hoc test (Tukey's test). Results: Group IV showed higher resistance to fracture than other groups significantly. There was a nonsignificant difference in fracture force between Group I, Group II, and Group III. Group V showed the least fracture resistance than other groups. Conclusion: Based on this in vitro study, TotalFill bioceramic-based sealer was more effective when compared with other sealers and the unobturated group showed the lowest mean fracture resistance. Clinical significance: The use of bioceramic sealer with BC cones enhanced the fracture resistance of endodontically treated teeth.