Switzerland recently introduced PROFILES, a revised version of its national outcomes reference framework for the undergraduate medical curriculum. PROFILES is based on a set of competencies adapted from the CanMEDS framework and nine entrustable professional activities (EPAs) that students have to be able to perform autonomously in the context of a predefined list of clinical situations. The nationwide implementation of such a competency- and EPA-based approach to medical education is a complex process that represents an important change to the organisation of undergraduate training in the various medical schools. At the same time, the concepts underlying PROFILES also have to be reflected at the level of the Federal Licencing Examination (FLE) and the national accreditation process. The vice-deans for education mandated a Swiss Working Group for PROFILES Implementation (SWGPI) to elaborate a guide presenting the principles and best practices based on the current scientific literature, to ensure the coherence between the future developments of the medical curricula and the evolution of the FLE, and to propose a coordinated research agenda to evaluate the implementation process. On the basis of the literature and analysis of our national context, we determined the key elements important for a successful implementation. They can be grouped into several areas including curricular design and governance, the assessment system and entrustment process, faculty development and change management. We also identified two dimensions that will be of particular importance to create synergies and facilitate exchange between the medical schools: a systematic approach to curriculum mapping and the longitudinal integration of an e-portfolio to support the student learning process. The nationwide collaborative approach to define strategies and conditions for the implementation of a new reference framework has allowed to develop a shared understanding of the implications of PROFILES, to promote the establishment of Swiss mapping and e-portfolio communities, and to establish the conditions necessary for ensuring the continuous alignment of the FLE with the evolving medical curricula.