BACKGROUND: Socio-economic inequalities in health have been in the public agenda for decades. General practice has an influential role to play in mitigating the impact of inequalities especially regarding chronic conditions. At the moment, general practice is dealing with serious challenges in relation to workforce shortages, increasing workload and the impact of the COVID-19 pandemic. It is important to identify effective ways so that general practice can play its role in reducing health inequalities. OBJECTIVES: We explored what types of interventions and aspects of routine care in general practice decrease or increase inequalities in health and care-related outcomes. We focused on cardiovascular disease, cancer, diabetes and/or chronic obstructive pulmonary disease. We explored for whom these interventions and aspects of care work best, why, and in what circumstances. Our main objective was to synthesise this evidence into specific guidance for healthcare professionals and decision-makers about how best to achieve equitable general practice. DESIGN: Realist review. MAIN OUTCOME MEASURES: Clinical or care-related outcomes by socio-economic group, or other PROGRESS-Plus criteria. REVIEW METHODS: Realist review based on Pawson's five steps: (1) locating existing theories, (2) searching for evidence, (3) selecting articles, (4) extracting and organising data and (5) synthesising the evidence. RESULTS: Three hundred and twenty-five studies met the inclusion criteria and 159 of them were selected for the evidence synthesis. Evidence about the impact of general practice interventions on health inequalities is limited. To reduce health inequalities, general practice needs to be: • connected so that interventions are linked and coordinated across the sector; • intersectional to account for the fact that people's experience is affected by many of their characteristics; • flexible to meet patients' different needs and preferences; • inclusive so that it does not exclude people because of who they are; • community-centred so that people who receive care engage with its design and delivery. These qualities should inform action across four domains: structures like funding and workforce distribution, organisational culture, everyday regulated procedures involved in care delivery, interpersonal and community relationships. LIMITATIONS: The reviewed evidence offers limited detail about the ways and the extent to which specific interventions increase or decrease inequalities in general practice. Therefore, we focused on the underpinning principles that were common across interventions to produce higher-level, transferrable conclusions about ways to achieve equitable care. CONCLUSIONS: Inequalities in general practice result from complex processes across four different domains that include structures, ideas, regulated everyday procedures, and relationships among individuals and communities. To achieve equity, general practice needs to be connected, intersectional, flexible, inclusive and community-centred. FUTURE WORK: Future work should focus on how these five essential qualities can be better used to shape the organisational development of future general practice. STUDY REGISTRATION: This trial is registered as PROSPERO CRD42020217871. FUNDING: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR130694) and is published in full in ; Vol. 12, No. 7. See the NIHR Funding and Awards website for further award information.