<ns4:p><ns4:bold>Background: </ns4:bold>Environmental improvement is a priority for urban sustainability and health and achieving it requires transformative change in cities. An approach to achieving such change is to bring together researchers, decision-makers, and public groups in the creation of research and use of scientific evidence.</ns4:p><ns4:p> <ns4:bold>Methods: </ns4:bold>This article describes the development of a programme theory for Complex Urban Systems for Sustainability and Health (CUSSH), a four-year Wellcome-funded research collaboration which aims to improve capacity to guide transformational health and environmental changes in cities.</ns4:p><ns4:p> <ns4:bold>Results: </ns4:bold>Drawing on ideas about complex systems, programme evaluation, and transdisciplinary learning, we describe how the programme is understood to “work” in terms of its anticipated processes and resulting changes. The programme theory describes a chain of outputs that ultimately leads to improvement in city sustainability and health (described in an ‘action model’), and the kinds of changes that we expect CUSSH should lead to in people, processes, policies, practices, and research (described in a ‘change model’).</ns4:p><ns4:p> <ns4:bold>Conclusions: </ns4:bold>Our paper adds to a growing body of research on the process of developing a comprehensive understanding of a transdisciplinary, multiagency, multi-context programme. The programme theory was developed collaboratively over two years. It involved a participatory process to ensure that a broad range of perspectives were included, to contribute to shared understanding across a multidisciplinary team. Examining our approach allowed an appreciation of the benefits and challenges of developing a programme theory for a complex, transdisciplinary research collaboration. Benefits included the development of teamworking and shared understanding and the use of programme theory in guiding evaluation. Challenges included changing membership within a large group, reaching agreement on what the theory would be ‘about’, and the inherent unpredictability of complex initiatives.</ns4:p>