Purpose: Information Technologies and Knowledge-based Systems can significantly improve the management of complex distributed health systems, where supporting multidisciplinarity is crucial and communication and synchronization between the different professionals and tasks becomes essential. This work proposes the use of the ontological paradigm to describe the organizational knowledge of such complex healthcare institutions as a basis to support their management. The ontology engineering process is detailed, as well as the way to maintain the ontology updated in front of changes. The paper also analyzes how such an ontology can be exploited in a real healthcare application and the role of the ontology in the customization of the system. The particular case of senior Home Care assistance is addressed, as this is a highly distributed field as well as a strategic goal in an ageing Europe. Materials and methods: The proposed ontology design is based on a Home Care medical model defined by an European consortium of Home Care professionals, framed in the scope of the K4Care European project (FP6). Due to the complexity of the model and the knowledge gap existing between the – textual – medical model and the strict formalization of an ontology, an ontology engineering methodology (On-To-Knowledge) has been followed. Results: After applying the On-To-Knowledge steps, the following results were obtained: the feasibility study concluded that the ontological paradigm and the expressiveness of modern ontology languages were enough to describe the required medical knowledge; after the kick-off and refinement stages, a complete and non-ambiguous definition of the Home Care model, including its main components and interrelations, was obtained; the formalization stage expressedHCmedical entities in the form of ontological classes, which are interrelated by means of hierarchies, properties and semantically rich class restrictions; the evaluation, carried out by exploiting the ontology into a knowledge-driven e-health application running on a real scenario, showed that the ontology design and its exploitation brought several benefits with regards to flexibility, adaptability and work efficiency from the end-user point of view; for the maintenance stage, two software tools are presented, aimed to address the incorporation and modification of healthcare units and the personalization of ontological profiles.Conclusions: The paper shows that the ontological paradigm and the expressiveness of modern ontology languages can be exploited not only to represent terminology in a nonambiguous way, but also to formalize the interrelations and organizational structures involved in a real and distributed healthcare environment. This kind of ontologies facilitates the adaptation in front of changes in the healthcare organization or Care Units, supports the creation of profile-based interaction models in a transparent and seamless way, and increases the reusability and generality of the developed software components. As a conclusion of the exploitation of the developed ontology in a real medical scenario, we can say that an ontology formalizing organizational interrelations is a key component for building effective distributed knowledge-driven e-health systems.