Health guidelines are important resources for informing decisions made by health practitioners, patients, caregivers, policymakers, and other interest-holders. Interest-holder engagement in health guideline development can improve the relevance of recommendations, promote considerations of equity, and support implementation. To facilitate efficient and effective health guideline development, there is a need for a comprehensive, global, evidence-based guidance for interest-holder engagement in guideline development. This paper synthesises the barriers and facilitators to interest-holder engagement in guideline development. Several systematic reviews have examined the topic of interest-holder engagement in guideline development, but few have explicitly focused on barriers and facilitators to engagement and the majority of these were related to patients. With increased recognition of the value of broad interest-holder engagement, understanding the barriers and facilitators to interest-holder engagement is key to developing a relevant and inclusive health guideline. The objective of this review is to identify and synthesise the reported evidence on barriers and facilitators to interest-holder engagement in health guideline development. We address this objective through two research questions: 1. What are the reported barriers to interest-holder engagement in health guideline development across the 18 topics of the GIN-McMaster checklist? 2. What are the reported facilitators to interest-holder engagement in health guideline development across the 18 topics of the GIN-McMaster checklist? We searched five major electronic databases (MEDLINE (OVID), Cumulative Index to Nursing & Allied Health Literature (CINAHL; EBSCO), EMBASE (OVID), PsycInfo (OVID), Scopus, and Sociological Abstracts. We also conducted an extensive grey literature search using the websites of agencies who actively engage interest-holders in research and/or guideline-producing agencies, such as PCORI, WHO and GIN. We searched from database inception up to the 26th September, 2022. Backward and forward citation tracking was performed on included articles to identify other eligible studies. We included primary research studies which qualitatively reported on the barriers or facilitators to interest-holder engagement in health guideline development. This included qualitative or mixed method research studies using methods such as interviews, focus groups, or surveys to collect participant experiences; case studies of existing programmes; and process evaluation studies. We excluded non-empirical publications including commentaries and editorials. We excluded publications with incomplete data, including conference abstracts and protocols. We defined interest-holders as "any individual or group who is responsible for or affected by health- and healthcare-related decisions". We identified 10 types of interest-holders whose input can enhance the relevance and uptake of guidelines. We included studies that reported on the barriers or facilitators to engagement of one or several of these interest-holder groups at any step of the guideline development process. All identified citations from electronic databases were imported into Covidence for screening and selection. Documents identified through our grey literature search were managed and screened using an Excel spreadsheet. A two-part study selection process was used for all identified citations: (1) a title and abstract review and (2) full-text review. At each stage, teams of two review authors independently assessed all potential studies in duplicate using a priori inclusion and exclusion criteria. Data was extracted from each included article in duplicate and independently. We extracted information about study characteristics and methods. Additionally, we extracted qualitatively reported barriers and facilitators and conducted a framework analysis. We selected the Theoretical Domains Framework (TDF) for extracting our barriers and facilitator findings. Developed through a multidisciplinary consensus approach and subsequent validation, TDF consolidates overlapping behavioural theories into 14 domains encompassing 84 theoretical constructs, and provides a theoretical lens through which to view the cognitive, affective, social and environmental influences on behaviour and implementation. Two review authors conducted the analysis. Our qualitative evidence synthesis identified a total of 51 findings, encompassing 23 barriers and 28 facilitators to interest-holder engagement in health guideline development. While the large majority of reported evidence is about patient engagement, many findings are applicable to all interest-holder groups and should be considered by guideline developers who aim to apply a multi-interest-holder engagement approach. Many organisations that produce guidelines lack the resources to support interest-holder engagement. By implementing an organisational interest-holder engagement model, guideline developers can ensure that they have the necessary human and financial resources in place. The interest-holders which are recruited to a guideline project should be knowledgeable and experienced, and guideline developers should consider diverse perspectives, roles, and personal characteristics. Using a network approach for identification and recruitment can help identify appropriate and committed interest-holders. To prevent tokenistic engagement, guideline developers can promote the meaningful engagement of interest-holders by providing practical, technical and emotional support. This includes providing training to empower interest-holders and improve self-efficacy and confidence in guideline development skills. Training should focus on evidence-based methods such as systematic reviews and evidence-to-decision frameworks. Engagement throughout all stages of guideline development supports more meaningful engagement compared to occasional involvement. A skilled moderator/chair can manage group dynamics and support the contributions of all those involved in guideline development. They can also offer explanations and promote plain language as-needed. Finally, many interest-holders have limited time to contribute to guidelines, and developers should establish flexible processes and timelines, and consider interest-holders preferences for in-person and online engagement activities. Identifying and analysing barriers and facilitators to interest-holder engagement is important in order to optimise health guideline development. Knowing facilitators to engagement can support future interest-holder engagement work. More research is needed on the barriers that do not have potential facilitator solutions, to understand how to improve upon known challenges. This review calls for the development of training courses and tools to support and facilitate involvement of all interest-holders, both public and professionals. In addition, it calls for further research to be done with a focus on the dynamics of guideline development, perceived interactions within the group and their impact on decisions. Work should also be done to look at the implementation of guidelines and the influence of interest-holder engagement on uptake. What challenges do patients and other interest-holders face when creating health guidelines, and how can we support them? The review in brief: Health guidelines help many people, such as clinicians and patients, make decisions about healthcare. It is necessary to involve different types of people in the creation of health guidelines. This review summarises the challenges that people face when working together to create health guidelines and what kind of support helps them work together. Most of what we know about the experience of partnership when developing health guidelines is from patients. The main challenges facing patients are unclear roles, need for training and support, difficulty speaking up, and not having enough time to do the work. To support them, guideline developers should offer practical, technical and emotional support and work with flexible timelines and processes. More research is needed to understand the challenges faced by policymakers, practitioners, researchers and patients from different backgrounds and experiences. What challenges do patients and other interest-holders face when creating health guidelines, and how can we support them? Health guidelines are important documents that can help people, such as practitioners and patients, make decisions about healthcare. It is becoming more common to involve different types of people in the creation of health guidelines. We wanted to know what challenges people face when working together to create health guidelines, and what types of supports are useful. What did we do? We looked for literature that described people’s experiences when collaborating to create health guidelines. We specifically looked for information that described challenges they faced, how they overcame these challenges, and what type of supports they wished were in place. We were interested in documents that described ten different types of people who can contribute to the guideline development process, including patients, practitioners, and members of the public. We organised our results using a pre-existing checklist (GIN-McMaster Checklist for Guideline Development). What did we find? We found 40 documents that described challenges and ways to support people who are engaged in the guideline development process. Most of the evidence came from high-income countries and most of it was about patients and their experience being part of guideline development. These documents described how finding the right people to include in a guideline project can be challenging, since they need specific skills and knowledge or experience. People described not always understanding their role in the project, and needing more training and support in order to do their work. Organisations that develop guidelines did not always have the resources needed to support them. An important resource is the guideline chair, who leads the group discussions and can support everyone involved in creating the health guideline. The best way to support people is to provide them with choices and flexibility in how they engage in the guideline development process. People may prefer working in-person or online and need enough time to get the work done. What are the limitations of the evidence? Most of the evidence we found is about patients, and more research is needed about different interest-holders such as policy makers, health practitioners, and researchers. More information is also needed about how to involve people from diverse backgrounds, such as those who live in low-income settings. Additionally, we did not find evidence for all of the steps needed to create a guideline, such as priority setting. How up-to-date is this evidence? Evidence was included up to September 26, 2022.