Purpose: Zygomatic implants (ZIs) have been considered a reliable alternative treatment for patients with maxillary atrophy and/or maxillary defects. The use of a navigation system for assisting ZI placement could be a reliable approach for enhancing accuracy and safety. The purpose of this in vitro study was to evaluate the accuracy of a new dynamic surgical navigation system with its minimally invasive registration guide for quad zygomatic implant placement in comparison with a gold standard navigation approach. Materials and Methods: A total of 40 zygomatic implants were placed in 10 3D-printed models based on the CBCT scans of edentulous patients. For registration, a surgical registration guide with a quick response plate was used for the test group, and five hemispheric cavities as registered miniscrews in the intraoral area were used for the control group. In each model, a split-mouth approach was employed (two ZIs in bilateral zygomata) to test both systems. After ZI placement, a CBCT scan was performed and merged with pre-interventional planning. The deviations between planned and placed implants were calculated as offset basis, offset apical, and angular deviation and compared between the systems. Results: The offset basis, offset apical, and angular deviation were 1.43 ± 0.55 mm, 1.81 ± 0.68 mm, and 2.32 ± 1.59 degrees in the test group, respectively. For the control group, values of 1.48 ± 0.57 mm, 1.76 ± 0.62 mm, and 2.57 ± 1.51 degrees were measured without significant differences between groups (all P < .05). The accuracy of ZI positions (anterior and posterior) were measured without significant differences between groups. Conclusion: Two navigation systems with different registration techniques seem to achieve comparable acceptable accuracy for dynamic navigation of zygomatic implant placement. With the test group system, additional pre-interventional radiologic imaging and invasive fiducial marker insertion could be avoided.