Purpose: To evaluate the soft tissue changes of the face between two positions of occlusion: maximal intercuspal position (MIP) and physiologic rest position (RP). Materials and Methods: In this study, facial surface scans of 83 volunteers in two mandibular positions (MIP and RP) were obtained using a 3D optical scanner. On each 3D image, 21 cephalometric soft tissue landmarks were identified and then compared using t test for various facial parameters (widths, heights, depths, angles, and ratio). Additionally, a regional analysis of the facial surface differences in each patient between the two mandibular positions was performed using a whole scan shell best-fit method and the regional forehead best-fit method. Results: In MIP, facial heights with the nasion-gnathion distance shortened by approximately 1.2 mm (due to the vertical shrinkage of both lips together by 0.8 mm), and the mouth width was significantly widened, while other facial widths displayed no change. The labiomental angle and the upper vermilion arch were altered correspondingly, and regional analysis confirmed the findings with evident changes in the mandibular and subnasal areas with deviations amplified toward the facial midline. Conclusions: By applying 3D facial-scanning technology, this study displayed changes of facial appearance in different mandibular positions (MIP and RP), highlighting the need to instruct and monitor the patient’s mandibular position more consistently to achieve accurate and repeatable data in a 3D facial analysis.