OBJECTIVE Comparative studies of bone remodelling and mechanical stresses between inlay and onlay fixed partial dentures (FPD) are rather limited. The purpose of this paper was to evaluate the biological consequence in posterior mandibular bone and the mechanical responses in these two different prosthetic configurations. METHODS Three-dimensional (3D) finite element analysis (FEA) models are created to explore the mechanical responses for the inlay and onlay preparations within the same oral environment. Strain induced bone remodelling was simulated under mastication. The remodelling adopted herein relates the strain in the bone to the change of Hounsfield Unit (HU) value in proportion to the surface area density (SAD) of bony morphology, which allows directly correlating to clinical computerised tomography (CT) data. RESULTS The results show that both FPD designs exhibit a similar resultant change in bone mineral density (BMD) though the onlay configuration leads to a more uniform distribution of bone density. The inlay design results in higher mechanical stresses whilst allowing preservation of healthy tooth structure. CONCLUSIONS This study provides an effective means to further clinical assessment and investigation into biomechanical responses and long-term restorative outcome with different FPD designs. CONCLUSIONS Quantifying in vivo stress distributions associated with inlay/onlay FPDs can further supplement clinical investigations into prosthetic durability, FPD preparation techniques (i.e., taper angles, material development), consequent stress distributions and the ongoing biomechanical responses of mandibular bone.