Social Prescribing (SP) is an innovative solution to bridging the gap between primary health care and non-clinical supports and services within the community. SP enables general practitioners who identify health-related social problems to refer patients to a so-called link worker. The link worker provides personalized support and helps these patients to access community resources by addressing any barriers that may exist. SP is an approach to integrate health and social care and strengthen community orientation. SP thereby mitigates the effects of social determinants of health on health outcomes. However, SP has not been tailored to the needs of people in vulnerable situations yet and the effectiveness of SP to improve their access to health and care services remains unknown. The overall objective of SP-EU is to assess the potential of SP to promote and improve access to health and care services for people in vulnerable situations, focusing on three primary target groups: LGBTIQ persons, refugees and first-generation immigrants and older adults living alone. SP-EU follows a mixed-methods approach: SP adaptations will be co-created with the target groups, to adapt them to their specific needs and social contexts. A pragmatic randomized controlled trial will assess the effectiveness of the adapted SP to improve access by randomizing 1,776 patients in eight EU countries to receive SP or care as usual. A qualitative analysis in five European countries will explore enabling and limiting factors to the implementation of SP from different stakeholders’ perspectives. Additionally, we will communicate and disseminate results and translate them into policy action. SP-EU will enable health care systems to implement SP as a scalable, safe, cost-effective and people-centred solution to provide equal access to sustainable care. Thus, SP-EU will enable the transformation of European health care systems to equitable, community-based, people-centred and integrated health care.