Purpose: Real-time surgical navigation has been increasingly applied in implant placement. The initial registration procedures were found to substantially affect the overall accuracy, but the number and distribution of fiducial markers are yet undetermined. This study aimed to determine the minimal number and optimal distribution of fiducial markers to achieve clinically acceptable accuracy in surgical navigation for zygomatic implant placement by systematically analyzing the effects of different setups of fiducial markers on target registration error (TRE). Materials and Methods: A maxillary phantom with bone-anchored fiducial markers was scanned using cone beam computed tomography, followed by data processing on Brainlab, a commercially available navigation system. A total of 10 miniscrews were inserted in the edentulous maxilla for the configuration of the fiducial markers, with another two miniscrews as implant targets to assess the TRE in zygomatic bone. Data were then collected in nine configurations with distinct fiducial numbers and positions. Statistical analyses were performed with SPSS. Results: The accuracy of the surgical navigation system was found to depend on both the number and the position of fiducial markers. No significant difference was observed in accuracy among groups with eight fiducials and with a polygon span distribution (P > .05). When the fiducial number decreased to less than six, the markers inserted in a regular triangle were more precise than those in an inverse triangle configuration. When the number of fiducials was five with a polygonal distribution, a low TRE value of 0.59 mm was detected, which was comparable to the accuracy with more than eight fiducials in this study. Conclusion: A scattered distribution with a polygon span with at least five fiducial markers in the edentulous maxilla for registration seems to achieve acceptable TRE values with high accuracy for navigation in zygomatic implant placement. Keywords: accuracy, edentulous, navigation system, registration, zygomatic implant