Objectives Healthcare leaders around the world are calling for radical, transformational change of our health and care systems. This will be a difficult and complex task. In this article, we examine case studies in which transformational change has been achieved, and seek to learn from these experiences.Methods We used the case study method to investigate examples of transformational change in healthcare. The case studies were identified from preliminary doctoral research into the transition towards future sustainable health and social care systems. Evidence was collected from multiple sources, key features of each case study were displayed in a matrix and thematic analysis was conducted. The results are presented in narrative form.Results Four case studies were selected: two from the US, one from Australia and one from the UK. The notable features are discussed for each case study. There were many common factors: a well communicated vision, innovative redesign, extensive consultation and engagement with staff and patients, performance management, automated information management and high-quality leadership.Conclusions Although there were some notable differences between the case studies, overall the characteristics of success were similar and collectively provide a blueprint for transformational change in healthcare.What is known about the topic? Healthcare leaders around the world are calling for radical redesign of our systems in order to meet the challenges of modern society.What does this paper add? There are some remarkable examples of transformational change in healthcare. The key factors in success are similar across the case studies.What are the implications for practitioners? Collectively, these key factors can guide future attempts at transformational change in healthcare.