Background: Integrated utilisation of digital health data has the power to transform healthcare to deliver more efficient and effective services, and the learning health system (LHS) is emerging as a model to achieve this. The LHS uses routine data from service delivery and patient care to generate knowledge to continuously improve healthcare. The aim of this project was to explore key features of a successful and sustainable LHS to inform implementation in an Academic Health Science Centre context.Methods: We purposively identified and conducted semi-structured qualitative interviews with leaders, experienced in supporting or developing data driven innovations in healthcare. A thematic analysis using NVivo was undertaken.Results: Analysis of 26 interviews revealed five themes thought to be integral in an effective, sustainable LHS: (1) Systematic approaches and iterative, continuous learning with implementation into healthcare contributing to new best-practice care; (2) Broad stakeholder, clinician and academic engagement, with collective vision, leadership, governance and a culture of trust, transparency and co-design; (3) Skilled workforce, capability and capacity building; (4) Resources with sustained investment over time and; (5) Data access, systems and processes being integral to a sustainable LHS. Conclusions: This qualitative study provides insights into the elements of a sustainable LHS across a range of leaders in data-driven healthcare improvement. Fundamentally, an LHS requires continuous learning with implementation of new evidence back into frontline care to improve outcomes. Structure, governance, trust, culture, vision and leadership were all seen as important along with a skilled workforce and sustained investment. Processes and systems to optimise access to quality data were also seen as vital in an effective, sustainable LHS. These findings will inform a co-designed framework for implementing a sustainable LHS within the Australian healthcare and Academic Health Science Centre context. It is anticipated that application of these findings will assist to embed and accelerate the use of routine health data to continuously generate new knowledge and ongoing improvement in healthcare delivery and health outcomes.