Background The past two decades have seen increasingly rapid advances in the field of diagnostic imaging technology. This has significantly contributed to the quality of medical care outcomes. However, a number of studies have found that 20%-50% of imaging requisitions are inappropriate and unjustified. This wastes the already meager resources and exposes patients to unnecessary radiation with increased risk of radiation induced cancers.Clinical Imaging Guidelines (CIGs) are evidence-based tools developed to support the imaging referrer’s decision-making process by choosing the most appropriate imaging investigation for a particular patient with a specific set of symptoms and signs. However, implementing CIGs has not been effective in several settings. Identifying factors that influence CIGs implementation could give an insight into the type of strategies to put in place before implementing CIGs This systematic review protocol is aimed at understanding barriers and facilitators that influence implementation of CIGs among medical professions. Review Methods The development of the systematic review protocol will follow Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA-P) (additional file 1) Key databases Pubmed (Medline) and Embase will be searched using relevant terms. The, experts in the field will be contacted for their opinion and references from included studies will also be searched Only literature written in the English language will be reviewed. All study designs will be included, and there will be no limit set by the year of publication. The criteria for inclusion will be those studies which document and discuss barriers and facilitators to implementing CIGs among medical professions. All identified studies will be screened by a single reviewer but Quality of the studies to be included and extraction of data will be independently performed by two reviewers. Any discrepancies will be resolved by consensus through discussion, with a 3rd reviewer as a tie breaker Pre-established categories of barriers and facilitators to implementing CIGs in practice from literature, will be used to assess content analysis Discussion The findings from this review will provide an insight and direction to the “champions” implementing adoption or adaption of CIGs, especially in Africa of what is ahead of them for proper planning The protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD42020136372.