Background: There are many dental manifestations of cleidocranial dysplasia (CCD). These include retained primary teeth, supernumerary teeth, and impacted permanent teeth.1 Additionally, these individuals may also have anterior crossbites, posterior crossbites, and reduced overbite.23 Patients with CCD often require extensive orthodontic treatment to erupt the impacted permanent dentition and often also require orthognathic surgery to correct the malocclusion. Additionally, some patients with CCD undergo prosthodontic replacement of impacted teeth rather than orthodontics, or a combination of prosthodontic and orthodontic treatment. This study focuses on whether individuals with CCD with certain malocclusion traits have a worse oral health related quality of life (OHQOL) than those without these malocclusion traits. Additionally, this study aims to determine if individuals with CCD that received orthodontic treatment with or without prosthodontics had a better OHQOL than those treated with prosthodontics alone. Methods: Individuals over the age of 15 with CCD were recruited to undergo an oral examination to assess malocclusion and number of missing teeth and to complete the OHIP-14 survey. This survey considered the following domains: Functional Limitation, Physical Pain, Psychological Discomfort, Physical Disability, Psychological Disability, Social Disability, and Handicap. Independent sample t-tests were performed to compare OHIP-14 scores in individuals with CCD with and without specific oral findings. Additionally, individuals with CCD who had completed their orthodontic treatment were asked about the duration of their orthodontic treatment, and if in hindsight, they would have preferred prosthodontic treatment alone. Results: Seventy-five individuals with CCD over the age of 15 underwent oral exams, and 61 of these individuals completed the OHIP-14 survey. Independent sample t-tests revealed that individuals with CCD who had posterior crossbites experienced significantly worse oral health-related quality of life (OHQOL) in the domain of physical pain (p = 0.015, 95% CI: [0.316, 2.750]). For those with anterior open bites, a significantly worse OHIP-14 score was observed in the domain of handicap (p = 0.046, 95% CI: [0.027, 2.919]). Anterior crossbites resulted in statistically significant worse OHIP-14 score in the functional limitation domain (p = 0.027, 95% CI: [0.149, 2.373]). Lastly, individuals who received only prosthodontic treatment and no orthodontic treatment reported significantly worse overall total OHIP-14 scores (p = 0.037, 95% CI: [0.685, 21.015]) and higher scores in physical pain (p = 0.038, 95% CI: [0.114, 3.981]), physical disability (p = 0.005, 95% CI: [0.872, 4.543]), and social disability (p = 0.020, 95% CI: [0.091, 3.398]). Nineteen individuals who completed their orthodontic treatment responded to the survey about their orthodontic treatment. Orthodontic treatment among these respondents took an average of almost ten years, and 40% of these respondents stated that they would have preferred prosthodontic treatment alone. Conclusion: Individuals with CCD who have anterior crossbites, posterior crossbites, or anterior open bites have statistically significantly worse OHQOL in specific domains compared to individuals with CCD without these malocclusions. Additionally, although 40% of individuals with CCD who had orthodontic treatment stated that they would have preferred prosthodontics alone, OHIP-14 results indicate that those who had received prosthodontics alone had statistically significant worse OHQOL.