Background: While health informatics recommendations on competencies and education serve as highly desirable corridors for designing curricula and courses, they cannot show how the content should be situated in a specific and local context. Therefore, global and local perspectives need to be reconciled in a common framework. Objectives: The primary aim of this study is therefore to empirically define and validate a framework of globally accepted core competency areas in health informatics and to enrich this framework with exemplar information derived from local educational settings. Methods: To this end, (i) a survey was deployed and yielded insights from 43 nursing experts from 21 countries worldwide to measure the relevance of the core competency areas, (ii) a workshop at the International Nursing Informatics Conference (NI2016) held in June 2016 to provide information about the validation and clustering of these areas and (iii) exemplar case studies were compiled to match these findings with the practice. The survey was designed based on a comprehensive compilation of competencies from the international literature in medical and health informatics. Results: The resulting recommendation framework consists of 24 core competency areas in health informatics defined for five major nursing roles. These areas were clustered in the domains data, information, knowledge, information exchange and information sharing, ethical and legal issues, systems life cycle management, management and biostatistics and medical technology, all of which showed high reliability values. The core competency areas were ranked by relevance and validated by a different group of experts. Exemplar case studies from Brazil, Germany, New Zealand, Taiwan/China, United Kingdom (Scotland) and the United States of America expanded on the competencies described in the core competency areas. Conclusions: This international recommendation framework for competencies in health informatics directed at nurses provides a grid of knowledge for teachers and learner alike that is instantiated with knowledge about informatics competencies, professional roles, priorities and practical, local experience. It also provides a methodology for developing frameworks for other professions/disciplines. Finally, this framework lays the foundation of cross-country learning in health informatics education for nurses and other health professionals.