Background: Evaluation of the biomechanical response of tooth with perforation repair is important to attain predictable prognosis. It may remain altered even after perforation repair due to the loss of tooth structure. Aim: The aim of this study is to assess and compare the effect of pulpal floor perforation repair of different sites with biodentine, on the biomechanical response of mandibular molar through 3-dimensional (3D) finite element analysis (FEA). Materials and Methods: Five different 3D models were constructed based on the site of perforation on the pulpal floor using cone-beam computed tomographic images of an extracted mandibular molar. Perforation size was standardized and simulated to be repaired with calcium silicate-based cement. A force of 200 N was applied simulating normal occlusal loads. Static linear FEA was performed using the Ansys FEA software. Tensile stresses were evaluated (P max ). Statistical Analysis Used: The data were evaluated using the independent t-test ( P = 0.05). Results: All the simulated models with perforation repair exhibited higher stress values than their equivalent sites in the control group. The P max values of the repaired models were highest in central furcal perforation, followed by buccal furcal perforation. However, there was no statistically significant difference in the stress accumulation among the different repaired perforation sites. Conclusion: The site of the pulpal floor perforation affected the stress distribution and accumulation. Central and buccal furcal perforation repairs on the pulpal floor with calcium silicate-based cement in mandibular molar are likely to have an increased risk of fracture.