Background: In response to policy recommendations, nine National Institute for Health Research (NIHR) Collaborations for Leadership in Applied Health Research and Care (CLAHRCs) were established in England in 2008, aiming to create closer working between the health service and higher education and narrow the gap between research and its implementation in practice. The Greater Manchester (GM) CLAHRC is a partnership between the University of Manchester and twenty National Health Service (NHS) trusts, with a five-year mission to improve healthcare and reduce health inequalities for people with cardiovascular conditions. This paper outlines the GM CLAHRC approach to designing and evaluating a large-scale, evidence- and theory-informed, context-sensitive implementation programme.Discussion: The paper makes a case for embedding evaluation within the design of the implementation strategy. Empirical, theoretical, and experiential evidence relating to implementation science and methods has been synthesised to formulate eight core principles of the GM CLAHRC implementation strategy, recognising the multi-faceted nature of evidence, the complexity of the implementation process, and the corresponding need to apply approaches that are situationally relevant, responsive, flexible, and collaborative. In turn, these core principles inform the selection of four interrelated building blocks upon which the GM CLAHRC approach to implementation is founded. These determine the organizational processes, structures, and roles utilised by specific GM CLAHRC implementation projects, as well as the approach to researching implementation, and comprise: the Promoting Action on Research Implementation in Health Services (PARIHS) framework; a modified version of the Model for Improvement; multiprofessional teams with designated roles to lead, facilitate, and support the implementation process; and embedded evaluation and learning.Summary: Designing and evaluating a large-scale implementation strategy that can cope with and respond to the local complexities of implementing research evidence into practice is itself complex and challenging. We present an argument for adopting an integrative, co-production approach to planning and evaluating the implementation of research into practice, drawing on an eclectic range of evidence sources.