Background Under a health reform after two decades, Primary Health Organisations (PHOs) in Australia were changed from Divisions of General Practice (DGP) to Medicare Locals (MLs). Following a review of Medicare Locals, in July 2015 Primary Health Networks (PHNs) replaced Medical Locals to potentially improve outcomes through supporting primary care and enhancing integration. Aims The aim of this paper was to gather front-line staff’s perspectives on MLs and identify any lessons applicable to PHNs. Methods A national purposive sample of 22 high-performing general practices representing all Australian states and territories was selected for semi-structured, face-to-face interviews, and a thematic analysis conducted. Results Fifty-three interviews were conducted: participants comprised 19 general practitioners (GPs), 18 practice managers (PMs), 15 practices nurses (PNs), and one community pharmacist. Most participants reflected on the difference between the DGP and MLs. Themes that emerged included ambiguity, community needs, professional development and education, communication and support, duplication in services and ignoring existing ones, recruitment and retention, and engagement and involvement. Conclusion Those MLs that did well continued in an expanded way the work DGP were doing beforehand and made a seamless transition. PHNs will need to build on the strengths of previous PHOs, and create locality structures and processes that maximise the potential for clinical engagement. They will actively guide the dialogue between related microsystems: to achieve this they will have to be clinically led, change management organisations.