Although quality of life (QOL) assessment is important in dentistry, it has not been fully investigated in orthodontic patients. We investigated the health-related generic QOL (entire body health) and disease specific QOL (oral health) in adult patients with malocclusions at the first visit. One hundred and twenty-seven orthodontic patients and 66 persons with normal occlusion were recruited for the study. The subjects were divided into the three following groups based on their treatment: 61 patients in need of surgical correction (SURG), 66 patients in need of non-surgical correction (NONS), and 66 control subjects with normal occlusion. Their dentofacial morphology was assessed using a specific Severity Score (SS), which was set up originally based on their cephalometric radiographs and their plaster models of arrangement of their teeth. The subjects also completed a generic QOL assessment questionnaire, the SF-36, and two disease-specific QOL instruments. The patients with malocclusions, especially SURG, had lower disease-specific QOL, although the generic QOL was equal to that of control subjects. Furthermore, in patients with the same severity of dentofacial deformities, especially SS 4 and SS 5, the borderline cases of surgical correction and non-surgical correction, there were differences between SURG and NONS in some items of the QOL. The severity of malocclusion evidently plays an important role in patients' choice of treatment, but also QOL appeared to play a significant role. The QOL assessment may contribute to the selection of the best treatment for improving QOL, especially for borderline cases with moderate degrees of orthodontic abnormality.