The aim of this paper is to examine the approach taken to regionalization in Ontario, Canada, and its impact on health system performance as perceived by managers and clinicians. This is a qualitative study, with thematic analysis, based on interviews with 23 managers and clinicians working in primary healthcare and emergency care in two regions of Ontario. Our findings demonstrate that both sets of actors see regional structures as contributing significantly to improving their respective health system although they also identify areas that require improvement. Managers and clinicians agreed on propositions to focus on health determinants, major considerations specific to the local context (population, geography) and support for a three-level system with well-defined functions. However, they also expressed differing propositions about the political power of hospitals.