Introduction: In 2010, in a context of severe economic recession, the Basque Government launched the Strategy to tackle the challenge of chronicity in the Basque Country to transform the Basque health system to cope with the challenges of chronicity, ageing, health system fragmentation and sustainability in the long run. Methods: A realist evaluation has been conducted, and through a combination of research methods, information has been analysed to identify context, mechanisms and outcomes. The research provides a snapshot of the experience of a system-wide, complex health system transformation, which aims to identify 'what has worked, for whom and under what circumstances'. Twenty-two semi-structured interviews held between June 2015 and December 2016, allowed us to obtain both retrospective and real-time accounts on the transformation phenomenon. Results: Research pointed out that system-wide transformation requires time, effort, leadership, vision and narrative, as well as commitment, inclusiveness, collaborative decision-making processes with local implementers, 'muddling through' and constant learning. Key levers to shake and shift the health and social care systems towards closer alignment, coordination and integration to meet the needs of people include promoting collaborative relationships between health professionals to ensure care continuity, developing new staff roles, investing in integrated electronic health records, stratifying the population by risk and facilitating bottom-up innovation. Discussion: Research has shown that system-wide changes in health and social care have been viable in the Basque Health System, although the interplay between context, mechanisms and outcomes is more complex than expected, leading to many unexpected factors, patterns and relationships.