Background: Health economic evaluation is a methodology to maximize health benefits and minimize opportunity costs and is of increasing importance in informing resource allocation decisions in healthcare., Objective: This systematic review aims to assess the availability and quality of economic evaluations of any orthodontic interventions and summarize the conclusions of these studies., Search Methods: A thorough search of the literature was carried out including terms related to orthodontic interventions and economic evaluation between January 2000 and February 2022. MEDLINE, EMBASE, SCOPUS, Web of Science, NHS Economic Evaluation Database, and Cochrane were searched. Grey literature was searched and further hand-searching was performed on the reference lists of relevant systematic reviews., Selection Criteria: Studies on cleft lip and palate surgery and sleep apnoea were excluded due to the multi-disciplinary nature of these conditions which might alter the applicability of the result to orthodontic interventions. Two independent reviewers selected studies for inclusion., Data Collection and Analysis: Data extraction was carried out through full text analysis of included studies by two authors. The quality of each study was assessed according to the Drummond 10-point Checklist and the National Institute for Health and Care Excellence (NICE) Quality Appraisal Checklist for Economic Evaluations. Characteristics and conclusions of included articles were descriptively summarized., Results: Sixteen articles met inclusion criteria. Most of the included articles were trial-based studies, with only one model-based study. Orthodontic interventions assessed included crossbite correction, functional appliance treatment and orthognathic surgery. Most studies were carried out in Europe and specifically in Sweden. The quality of included studies was generally low with 69% of studies reported as having serious limitations according to the NICE Checklist., Conclusion: This review highlighted a lack of economic evaluations for orthodontic interventions, and limitations of existing economic evaluations. Recommendations on future research are provided., Registration: The protocol for the systematic review was registered on the NIHR Database (www.crd.york.ac.uk/prospero, CRD42021220419)., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)