Lean in healthcare has continued to attract practitioner and research interest over the past two decades yet lacks evidence of sustained application. This longitudinal case study examines Lean healthcare interventions through the lens of Programme Theory, to provide an understanding of the design and implementation of a Lean programme. Through a qualitative single case study of an NHS organisation implementing Lean, content analysis of 70 reports from a 6-year period was undertaken and supported by interview data from 12 respondents involved in Lean initiatives. Through Programme Theory, we identify contextual moderators, internal and external, informing the design and development of Lean efforts. The key to successful and sustained Lean efforts is staff acceptance of the Programme Theory for delivering and maintaining outcomes. This has been identified as a key social determinant for Lean sustainability. Results from the research provide practical implications for designing a programme that accommodates resource challenges while incorporating multiple contextual drivers. The case study highlights an organisation’s Lean journey and the best practices that evolved; however, further longitudinal investigations are required to validate the findings.