Design A prospective interdisciplinary, multi-centre, cohort study. Cohort selection A total of 250 patients were recruited from three university departments of orthodontics and one orthodontic dental practice. The cohort size was decided by a sample size calculation performed and the participants were selected over 14 months. Four psychological questionnaires were used, each targeting specific psychological characteristics, combined with orthodontic assessments. Only questionnaires in English, with German translations, were chosen for international comparability. The COHIP-19 was used to assess Oral Health Related Quality of Life (OHRQoL), the KIDSCREEN-10 index was used to assess HRQoL, the RSES was used to assess self-esteem and the SDQ was used for behavioral problems. To record the orthodontic parameters, standardised orthodontic diagnosis consisted of detailed anamnesis, functional diagnosis, extra-oral photos, an orthopantomogram, lateral cephalomentrics and plaster impressions. The same assessor examined the questionnaires and the orthodontic measurements. Data analysis Statistical programme (SPSS) was used to assess the data. Simple linear regression models were tested to assess the predictive values of all the specific orthodontic parameters individually (= predictors) on the COHIP-G19 (= criterion). Further to this, multiple linear regression analysis was used to assess which of the independent predictors can be assessed in combination to relate to OHRQoL. Results The questionnaire was completed by 248 participants. From the simple linear regression, there was a statistically significantly impact on COHIP-G19 score in patients with competent lip closure, straight chin position, little-index-upper, overjet, overbite and ANB. For the multiple linear regression analysis, age, KIDSCREEN-10 index, RSES, SDQ and all six orthodontic parameters that had a statistically significant impact on COHIP-G19 (P <0.05) in the simple linear regression were assessed. Of these five (SDQ, KIDSCREEN-10, overjet, little-index-upper and overbite) parameters resulted in a multi-linear regression model that was statistically significant and explained 32.3% of the total variance in OHRQoL. Adding additional parameters did not significantly improve the R2-change. Conclusions Further longitudinal studies are required to investigate if the treatment of these malocclusions also improves the OHRQoL of children and adolescents. © 2020, British Dental Association.