Abstract The European Union and Latin America and the Caribbean regions have enjoyed privileged relations since the first bi-regional Summit of Heads of State and Government, held in Rio de Janeiro, Brazil, in 1999, and the lunching of a Strategic Partnership. Health research stands as one of the major areas of research and development expenditure in both regions and has also been the focus of roughly 30% of all bilateral cooperation agreements and programmes. EU-LAC Health, a project funded by the European Union from 2011 to 2017, had the main objective to develop a consensus roadmap to enhance and coordinate the bi-regional collaboration between the European Union member states and Latin America and Caribbean countries in health research. From April 2013, EU-LAC Health has also supported the Working Group on Health created and designated by decision-makers at the highest political level to implement a bi-regional Join Initiative on Research and Innovation. This article collects and summarises the context, methodology (series of workshops, surveys and iterative deskwork by multiple bi-regional stakeholders) of this project, as well as the main outputs of (1) definition of a strategic roadmap, containing a scientific research agenda, to guide policy-makers in equitable and collaborative health research and innovation; (2) launching of the Joint Initiative on Health Research and Innovation, with the vision of being the reference body on the bi-regional health research and innovation collaboration; and (3) funding of 13 bi-regional health research and innovation projects. EU-LAC Health represents a successful example of bi-regional collaboration and the emerging networks and expertise gathered during the lifetime of the project have the potential to tackle common health challenges affecting the quality of life of citizens from the two regions and beyond. The project has also paved the way for more specific bi-regional initiatives such as a new initiative for bi-regional collaboration in personalised medicine that is being arranged by the partnership. Furthermore, it can inspire future initiatives for bi-regional research collaboration on other fields.