To investigate whether patients with obstructive sleep apnea (OSA) have abnormalities in their craniofacial and upper airway (UA) structures compared with normal subjects, cephalometric comparisons were systematically performed in both the upright and the supine positions in subjects with and without OSA, who were then grouped according to their craniofacial skeletal type and gender. A total of 347 patients with OSA and 101 control subjects were divided into male and female groups and then classified into Class I (CI), Class II, Division 1 (CII/1), Class II, Division 2 (CII/2), and Class III (CIII) skeletal subtypes. In the upright position, the most atypical craniofacial and UA structure was shown in male patients with CI OSA. In patients with OSA, the degree of UA abnormalities was less in the supine position regardless of skeletal subtype. In the supine position, the most atypical craniofacial and UA structure was also shown in male patients with CI OSA; there were no significant differences between male patients with CII/2 OSA and control subjects or between female patients with CI OSA and control subjects. With a change in body position from upright to supine, distinctive changes in the UA structure in both patients with OSA and control subjects occurred, according to skeletal subtype and gender. We conclude that there are a series of characteristics of craniofacial and UA structure that differ between patients with OSA and control subjects matched for skeletal subtype and gender. These differences may predispose to UA obstruction during sleep in patients with OSA.