AbstractThis study aimed to understand the effect of physiological and dental implant‐related parameter variations on the osseointegration for an implant‐supported fixed prosthesis. Eight design factors were considered (implant shape, diameter, and length; thread pitch, depth, and profile; cantilever [CL] length and implant‐loading protocol). Total 36 implantation scenarios were simulated using finite element method based on Taguchi L36 orthogonal array. Three patient‐specific bone conditions were also simulated by scaling the density and Young's modulus of a mandible sample to mimic weak, normal, and strong bones. Taguchi method was employed to determine the significance of each design factor in controlling the peri‐implant cortical bone microstrain. For normal bone condition, CL length had the maximum contribution (28%) followed by implant diameter (18%), thread pitch (14%), implant length (8%), and thread profile (5%). For strong bone condition, CL and implant diameter had equal contribution (32%) followed by thread pitch (7%) and implant length (5%). For weak bone condition, implant diameter had the highest contribution (31%) followed by CL length (30%), thread pitch (11%) and implant length (8%). The presence of distal CL in dental framework was found to be the most influential design factor, which can cause high strain in the cervical cortical bone. It was seen that implant diameter had more effect compared to implant length toward peri‐implant bone biomechanical response. Implant‐loading time had no significant effect towards peri‐implant bone biomechanical response, signifying immediate loading is possible with sufficient mechanical retention.