The specialty of orthodontics aims to optimize patients’ skeletal and dental relationships, creating a harmonious orofacial complex and improving facial aesthetics and occlusal function. One common orthodontic problem is transverse maxillary constriction. Clinically, a transverse deficiency in the upper jaw presents as a narrow palate, dental crowding, crossbite, or a combination of these findings. If this orthodontic problem is diagnosed during the primary or mixed dentition years, it can be readily corrected with rapid palatal expansion. However, adult patients may also present with transverse maxillary constriction, which at this stage of skeletal maturation, requires more invasive treatment. Two treatment options that can address transverse deficiency in non-growing patients are surgically-assisted rapid palatal expansion (SARPE) and microimplant-assisted-rapid-palatal Expansion (MARPE). The MARPE technique involves the use of a maxillary skeletal expander (MSE) appliance anchored to the maxilla with mini-screws, applying expansile forces directly to the skeleton, rather than distributing them across the palate and dentition. Symmetric mid-palatal sutural separation is the anticipated therapeutic effect; however, midfacial changes may occur at other circummaxillary sutures. MARPE treatment outcomes must be evaluated clinically and radiographically. CBCT is the radiographic imaging modality of choice for patients treated with MARPE because of the effects that occur in all three planes of space. Mid-palatal suture measurements, and an abundance of additional information, can be obtained from 3D imaging analysis. The current evidence base surrounding clinical considerations of MSE placement for MARPE therapy is limited. The primary goal of this study was to assess if the skeletal position of MSE mini-screw/temporary anchorage device (TAD) placement influences the magnitude of mid-palatal suture separation and/or is associated with asymmetric skeletal changes during MARPE therapy, using CBCT imaging. We hypothesized that significant differences in mini-screw angulation relative to the palatal plane and the anteroposterior position of the MSE appliance in the hard palate may be associated with asymmetric mid-palatal suture separation. Subjects were grouped based on magnitude of asymmetric separation at the mid-palatal suture. Circummaxillary suture separation symmetry was compared between groups, along with anteroposterior positioning of the appliance, and mini-screw angulation. Our data analyses showed that the only statistically significant correlation for right and left suture separation occurred at the medial pterygoid plate suture in subjects with symmetric mid-palatal suture separation. Analysis of MSE placement and mini-screw angulation in all subjects revealed that the anteroposterior position of the mini-screws is associated with asymmetric expansion, while TAD angulation was not significant. Our findings provide guidance for clinicians’ placement of the MSE appliance in the hard palate. Careful planning and execution of MARPE therapy is likely to lead to improved predictability of mid-palatal suture separation and subsequent changes to other circummaxillary structures.