Objectives: To improve the provision of health care, academics can be asked to collaborate with clinicians, and clinicians with patients. Generating good evidence on health care practice depends on these collaborations working well. Yet such relationships are not the norm. We examine how social science research and health care improvement practice were linked through a programme designed to broker collaborations between clinicians, academics, and patients to improve health care – the UK National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for Northwest London. We discuss the successes and challenges of the collaboration and make suggestions on how to develop synergistic relationships that facilitate co-production of social science knowledge and its translation into practice. Methods: A qualitative approach was used, including ethnographic elements and critical, reflexive dialogue between members of the two collaborating teams. Results: Key challenges and remedies were connected with the risks associated with new ways of working. These risks included differing ideas between collaborators about the purpose, value, and expectations of research, and institutional opposition. Dialogue between collaborators did not mean absence of tensions or clashes. Risk-taking was unpopular – institutions, funders, and partners did not always support it, despite simultaneously demanding ‘innovation’ in producing research that influenced practice. Conclusions: Our path was made smoother because we had funding to support the creation of a ‘potential space’ to experiment with different ways of working. Other factors that can enhance collaboration include a shared commitment to dialogical practice, a recognition of the legitimacy of different partners’ knowledge, a long timeframe to identify and resolve problems, the maintenance of an enabling environment for collaboration, a willingness to work iteratively and reflexively, and a shared end goal. © The Author(s) 2020.