Cardioplegia is fundamental to the surgical repair of congenital heart defects by protecting the heart against ischaemia-reperfusion injury, characterised by low cardiac output and troponin release in the early postoperative period. The immature myocardium exhibits structural, physiological, and metabolic differences to the adult heart, with a greater sensitivity to calcium overloadmediated injury during reperfusion. del Nido cardioplegia was specifically designed to protect the immature heart, is widely used in North America, and may provide better myocardial protection in children; however, it has not been commercially available in the United Kingdom, where most centres use St Thomas' blood cardioplegia. There are no phase III clinical trials in children to support one solution over another and this lack of evidence, combined with variations in practice, suggest the presence of clinical equipoise. The best cardioplegia solution for use in children, and the impact of age and other clinical factors, remains unknown.In this Hunterian lecture, I propose an evidence-based strategy to improve myocardial protection during cardiac surgery in children through 1) conducting multi-centre clinical trials of established techniques; 2) improving our knowledge of ischaemia-reperfusion injury in the setting of cardioplegic arrest; 3) applying this to drive innovation, moving beyond current cardioplegia solutions; 4) empowering personalised medicine, through combining clinical and genomic data, including ethnic diversity; and 5) understanding the impact of cardioplegic arrest on the late outcomes that matter to patients and their families.