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Large-scale quality improvement programmes (QIPs) have diverse factors that may influence their success and can undergo rapid changes throughout their lifecycle. The COllaboratioN on QUality improvement initiative for achieving Excellence in STandards of COPD care (CONQUEST) programme has recently been implemented in primary care practices in the UK. The CONQUEST programme aims to identify patients with already diagnosed and undiagnosed COPD at high risk of COPD-related adverse outcomes and optimize their management. CONQUEST has been successful in identifying COPD patients who may represent an outsized opportunity to improve patient outcomes and healthcare utilization, whilst focusing on relatively few patients per primary care practice. This paper reviews the steps involved in implementing CONQUEST in the UK, focussing on the challenges encountered, the solutions used to overcome these challenges barriers, and the lessons learned for the implementation of QIPs more widely. Key lessons from this process include that QIPs need to be designed with the flexibility to adapt to multiple and different local contexts, that early monitoring of data across the lifecycle of a QIP allows efficient detection of issues and troubleshooting, and that planning for allocation of limited resources to a QIP is essential for real-world implementation. The problems and solutions described here are applicable to QIPs in a wide variety of high-risk diseases and different healthcare settings.