Background: Sophisticated guided surgery has not been implemented into total joint replacement-surgery (TJR) of the temporomandibular joint (TMJ) so far. Design and in-house manufacturing of a new advanced drilling guide with vector and length control for a typical TJR fossa component are described in this in vitro study, and its accuracy/utilization was evaluated and compared with those of intraoperative real-time navigation and already available standard drilling guides. Methods: Skull base segmentations of five CT-datasets from different patients were used to design drilling guides with vector and length control according to virtual surgical planning (VSP) for the TJR of the TMJ. Stereolithographic models of the skull bases were printed three times for each case. Three groups were formed to compare our newly designed advanced drilling guide with a standard drilling guide and drill-tracking by real-time navigation. The deviation of screw head position, screw length and vector in the lateral skull base have been evaluated (n = 72). Results: There was no difference in the screw head position between all three groups. The deviation of vector and length was significantly lower with the use of the advanced drilling guide compared with standard guide and navigation. However, no benefit in terms of accuracy on the lateral skull base by the use of real-time navigation could be observed. Conclusion: Since guided surgery is standard in implant dentistry and other CMF reconstructions, this new approach can be introduced into clinical practice soon, in order to increase accuracy and patient safety.