BackgroundSafety-netting has become best practice when dealing with diagnostic uncertainty in primary care. Its use, however, is highly varied and a lack of evidence-based guidance on its communication could be harming its effectiveness and putting patient safety at risk.ObjectiveTo use a realist review method to produce a programme theory of safety-netting, that is, advice and support provided to patients when diagnosis or prognosis is uncertain, in primary care.MethodsFive electronic databases, web searches, and grey literature were searched for studies assessing outcomes related to understanding and communicating safety-netting advice or risk communication, or the ability of patients to self-care and re-consult when appropriate. Characteristics of included documents were extracted into an Excel spreadsheet, and full texts uploaded into NVivo and coded. A random 10% sample was independently double -extracted and coded. Coded data wasere synthesised and itstheir ability to contribute an explanation for the contexts, mechanisms, or outcomes of effective safety-netting communication considered. Draft context, mechanism and outcome configurations (CMOCs) were written by the authors and reviewed by an expert panel of primary care professionals and patient representatives.Results95 documents contributed to our CMOCs and programme theory. Effective safety-netting advice should be tailored to the patient and provide practical information for self-care and reconsultation. The importance of ensuring understanding and agreement with advice was highlighted, as was consideration of factors such as previous experiences with healthcare, the patient’s personal circumstances and the consultation setting. Safety-netting advice should be documented in sufficient detail to facilitate continuity of care.ConclusionsWe present 15 recommendations to enhance communication of safety-netting advice and map these onto established consultation models. Effective safety-netting communication relies on understanding the information needs of the patient, barriers to acceptance and explanation of the reasons why the advice is being given. Reduced continuity of care, increasing multimorbidity and remote consultations represent threats to safety-netting communication.