One of the most widely reported complications associated with temporomandibular joint (TMJ) prosthetic total joint replacement (TJR) surgery is condylar component screw loosening and instability. The objective of this study was to develop a musculoskeletal model of the human jaw to assess the influence of prosthetic condylar component orientation and screw placement on condylar component loading during mastication. A three-dimensional model of the jaw comprising the maxilla, mandible, masticatory muscles, articular cartilage, and articular disks was developed. Simulations of mastication and a maximum force bite were performed for the natural TMJ and the TMJ after prosthetic TJR surgery, including cases for mastication where the condylar component was rotated anteriorly by 0 deg, 5 deg, 10 deg, and 15 deg. Three clinically significant screw configurations were investigated: a complete, posterior, and minimal-posterior screw (MPS) configuration. Increases in condylar anterior rotation led to an increase in prosthetic condylar component contact stresses and substantial increases in condylar component screw stresses. The use of more screws in condylar fixation reduced screw stress magnitudes and maximum condylar component stresses. Screws placed superiorly experienced higher stresses than those of all other condylar fixation screws. The results of the present study have important implication for the way in which prosthetic components are placed during TMJ prosthetic TJR surgery.