BACKGROUND:Health economic evaluations are essential to support health care policy and investment decisions. To date, health economic evaluations in orthotics and prosthetics have focused on discrete components of an orthosis/prosthesis (e.g. a microprocessor controlled prosthetic knee joint) rather than the broader service provided by orthotist/prosthetists. As such, the contribution to orthotic/prosthetic policy and investment decisions is unclear. Whilst there are opportunities to conduct more informative health economic evaluations that describe the costs and benefits of the orthotic/prosthetic service, it is important that prospective research is informed by a critical review of the method design challenges and an understanding of how this research can be improved. The aim of this systematic review is to critically appraise the existing orthotic/prosthetic health economic evaluation literature and therefore determine evidence gaps, critical method design issues and the extent to which the literature informs orthotic/prosthetic policy and investment decisions. METHODS:A comprehensive range of databases-AMED, EMBASE, MEDLINE and PsychINFO, Cumulative Index of Nursing and Allied Health Literature (CINAHL), ProQuest Nursing and Allied Health, Web of Science, Cochrane Database of Systematic Reviews (CDSR) and specialty health economic databases-will be searched using National Library of Medicine Medical Subject Headings (MeSH) terms as well as the title, abstract, and keyword terms. Search terms related to the intervention (e.g. orthosis), including variants used by varying professional disciplines (e.g. brace), will be used in preference to defining the populations that use orthotic and prosthetic services (e.g. people living with rheumatoid arthritis). Search terms related to health economic evaluations will be guided by previously developed and tested search strings and align with recommendations by the Canadian Agency for Drugs and Technologies in Health. Articles meeting the inclusion criteria will be hand-searched for relevant citations, and a forward citation search using Google Scholar will also be conducted to identify early online articles not yet indexed in traditional databases. Original research published in the English language and after 1 January 2000 will be included. The Checklist for Health Economic Evaluation Reporting Standards (CHEERS) and the Consensus on Health Economic Criteria (CHEC)-Extended list will be used to appraise the methodological quality and identify sources of bias. Data extraction and appraisal will be conducted by one reviewer independently using appraisal instrument guidelines and a content specific decision aid with exemplars. A subsequent review by a second researcher will be undertaken to confirm the accuracy of the extraction and appraisal, and a final review by a third where consensus cannot be reached. The data will be extracted to a purpose-built data extraction template with decision-making guidelines to support consistency. Where possible, the findings of the review will be reported as a meta-analysis, although the heterogeneity of the literature will likely mean a narrative review that illuminates method design issues that contribute to imprecision and variation will be more appropriate. DISCUSSION:This protocol has been purposefully designed to summarise the existing evidence and appraise the methodological approaches used and the quality of the health economic evaluations in orthotics and prosthetics. What we learn from this review will be used to guide further work in this area and design more rigorous health economic evaluations into the future. SYSTEMATIC REVIEW REGISTRATION:PROSPERO CRD42018116910.