This study sought to assess the impact of posterior cross-bite on OHRQoL in young people aged 15-25 and to determine whether the impact on higher domains of Oral Health Impact Profile-14 (physical disability, psychological disability, social disability and handicap) is a direct function of the cross-bite or mediated through the lower domains of OHIP-14 (functional limitation, pain and discomfort).One hundred and forty-five young adults [72 cross-bite cases and 73 controls] aged 15-25 years, attending orthodontic clinics at the Faculty of Dentistry, Universiti Teknologi MARA participated in this study. Participants completed the OHIP-14 and had a clinical examination for cross-bite. Data analyses included descriptive statistics, t-test and bivariate and multivariate regression modelling.There was no significant difference between the case and control groups in gender, age and education level. The mean scores (±SD) for OHIP-14 total and all domains were significantly higher in cross-bite patients as compared to controls. The bivariate and multivariate regression analyses showed functional limitation was significantly associated with all the higher domains in all four models, whereas pain was only significantly associated with the psychological domain and discomfort was only significantly associated with the physical disability domain.The possession of a posterior cross bite has a significant association with OHRQoL especially on the functional limitation and psychological disability domains, among 15-25 years old young people. The relationship of cross-bite and lower domains of OHIP-14 with higher domains of OHIP-14 was in agreement with the relationships proposed by Locker's conceptual model of oral health.Patients with a cross bite were more limited in their oral functions and experienced greater psychological discomfort than did controls. It is possible that part of patients' rationale for seeking treatment would be to alleviate such impacts on their oral health related quality of life.