Partnership is a prominent approach to delivering healthcare globally, with advocates arguing that partnership has distinctive advantages over alternatives such as hierarchies or markets. There is much debate as to whether partnerships represent a distinctive mode of coordination in practice, however. Furthermore, despite evidence from diverse settings of the challenges of putting partnerships into practice, there has been little cross-pollination between literature from different fields. We bring together existing literature and two partnership case studies in the contrasting contexts of the UK National Health Service and an internationally-funded health intervention in Cambodia. The case studies were conducted between 2005 and 2008.Based on our synthesis of the literature, we propose an analytical distinction between instrumental and transformative partnerships, arguing that it is transformative partnerships that can deliver the unique advantages set out in theory. Comparative analysis of the cases illustrates that although both were able to achieve some valuable successes, they fell short of realising their transformative potential. We identify five common issues that impeded or facilitated transformative partnership-working, at micro, meso- and macro-levels: starting conditions; programme set-up; funding asymmetries and interdependence; accountability mechanisms; and relationships and distance from the field. Through systematic comparison we offer a more nuanced understanding of how programmes themselves create particular architectures for partnership, how underlying globalised institutional logics of managerialism promote instrumental partnerships, and how local-level, interpersonal relationships may help to overcome barriers to partnership's transformative potential.