Purpose <p>The purpose of this study was to evaluate differences in Oral Health-Related Quality of Life (OHRQoL) among orthognathic patients with different skeletal malocclusions before initiating orthodontic treatment.</p> Methods <p>150 patients were evaluated for OHRQoL at the Oral and Maxillofacial Surgery Department at Boston University Goldman School of Dental Medicine. OHRQoL was measured using: (1) Oral Health Impact Profile-14 (OHIP-14) for generic OHRQoL; (2) Orthognathic Quality of Life Questionnaire (OQLQ) for condition-specific OHRQoL; and (3) the 12-item oral quality of life instrument (12-item OQOL) for generic OHRQoL. Cephalometric measurements were used to categorize facial types then two-sample t-tests and one-way ANOVAs were employed to analyze OHRQoL across groups.</p> Results <p>OHIP-14, OQLQ, and 12-item OQOL baseline scores were statistically different between skeletal Class I, II, and III patients (<i>p</i> &lt; 0.05), with Class II patients showing the highest scores. No significant differences were found between vertical patterns (<i>p</i> &gt; 0.05).</p> Conclusion <p>OHRQoL is different between skeletal Class I, II, and III patients with Class II patients reporting lower quality of life.</p>