In children with mandibular hypoplasia, airway management is challenging. However, detailed cephalometric assessment data for this population are sparse. The aim of this study was to find risk factors for predicting difficult airways in children with mandibular hypoplasia, and compare upper airway anatomical differences using three-dimensional computed tomography (3D CT) between children with mandibular hypoplasia and demographically matched healthy controls. There were significant discrepancies in relative tongue position (P < 0.01) and anterior distance of the hyoid bone (P < 0.01) between patients with mandibular hypoplasia and healthy controls. All mandibular measures were significantly different between the two groups, except for the height of the ramus of the mandible. After adjusting for age and sex, the anterior distance of hyoid bone and inferior pogonial angle were significantly associated with a difficult airway (P = 0.01 and P = 0.02). Quantitative analysis of upper airway structures revealed significant discrepancies, including relative tongue position, hyoid distance, and mandible measures between patients with mandibular hypoplasia and healthy controls. The anterior distance of the hyoid bone and inferior pogonial angle may be risk factors for a difficult airway in patients with mandibular hypoplasia.