BACKGROUND: South Africa (SA) is in the process of implementing National Health Insurance (NHI), which will require co-ordination of health provision across sectors and levels of care. Clinical practice guidelines (CPGs) are tools for standardising and implementing care, and are intended to influence clinical decision-making with consequences for patient outcomes, health system costs and resource use. Under NHI, CPGs will be used to guide the provision of healthcare for South Africans. It is therefore important to explore the current landscape of CPG developers and development. OBJECTIVE: To identify and describe all CPGs available in the public domain produced by SA developers for the SA context. METHODS: We conducted a cross-sectional evaluation using a two-part search process: an iterative, electronic search of grey literature and relevant websites (161 websites searched), and a systematic search for peer-reviewed literature (PubMed) after publication year 2000. CPGs were identified, and data were extracted and categorised by two independent reviewers. Any discrepancies were referred to a third reviewer. Data extracted included a description of the developer, condition, and reporting of items associated with CPG quality. RESULTS: A search conducted in May 2017 identified 285 CPGs published after January 2000. Of those, 171 had been developed in the past 5 years. Developers included the national and provincial departments of health (DoH), professional societies and associations, ad hoc collaborations of clinicians, and the Council for Medical Schemes. Topics varied by developer; DoH CPGs focused on high-burden conditions (HIV/AIDS, tuberculosis and malaria), and other developers focused on non-communicable diseases. A conflict of interest statement was included in 23% of CPGs developed by societies or clinicians, compared with 4% of DoH CPGs. CONCLUSION: Accessing CPGs was challenging and required extensive searching. SA has many contributors to CPG development from the public and private sectors and across disciplines, but there is no formal co-ordination or prioritisation of topics for CPG development. Different versions of the CPGs were identified and key quality items were poorly reported, potentially affecting the usability and credibility of those available. There was substantial variation in CPG comprehensiveness and methodological approach. Establishing a national CPG co-ordinating unit responsible for developing standards for CPG development along with clinical quality standards, and supporting high-quality CPG development, is one essential step for moving forward with NHI.