To solve complex problems, researchers are increasingly working in large, integrated research programmes. Integration of projects within a single programme rather than supporting a range of individual, more autonomous projects, is supposed to lead to several benefits, including: creating and enhancing synergies amongst projects, improving collaboration and knowledge exchanges amongst researchers from different disciplines, realizing efficiency gains, and generating a higher return on investments in R&D. However, often these advantages are insufficiently realized in practice and large-scale integrated programs instead incur high overhead costs, frustrate researchers, and realize insufficient integration and collaboration. Why do integrated programmes sometimes fail to realize their lofty ambitions? In the present paper, we use the literature on governance, management studies, and organizational economics to analyse several key problems plaguing integrated programmes. We argue that these problems can be linked to the implementation of programme management systems and coordination mechanisms that are poorly aligned with the unique characteristics of integrated programmes. We develop guidelines for funding agencies and programme managers to implement systems and mechanisms that are a better fit for purpose and that enhance collaboration.