Introduction: Patients with severe mandibular prognathism frequently require orthognathic surgery to correct skeletal disharmony. Genetic and environmental factors are suggested in the etiology of mandibular prognathism, but the precise contribution of these factors is unknown. Methods: To clarify the impact of genetic factors on mandibular prognathism, we gave a questionnaire to 105 subjects with severe skeletal Class III mandibular prognathism who planned to undergo or had undergone orthognathic surgery. The questionnaire assessed mandibular prognathism in 3 generations of each subject’s family. All answers were confirmed in a careful interview that included differentiation of “maxillary deficiency” and “mandibular excess.” This is the first 3-generation family study of mandibular prognathism in orthognathically treated patients. Results: The average ANB, SNA, and SNB angles in the probands were −3.7°, 80.9°, and 84.6°, respectively. A total of 1480 family members were examined, and 11.2% had mandibular prognathism. Men were slightly more affected than women; 68.6% of families had at least 1 member other than the proband with mandibular prognathism. The affected ratio of first-degree relatives was more than twice that of second-degree relatives (17.5% and 7.6%, respectively). There was no difference in the occurrence between fathers and mothers of probands, and siblings showed a high affected ratio of 25.0%. Falconer’s heritability was calculated as 84.3% in first-degree relatives. Conclusions: A high occurrence of mandibular prognathism was seen in families of orthognathically treated skeletal Class III patients, suggesting a profound genetic influence.