Background: The specification of metadata in clinical and epidemiological study projects absorbs significant expense. The validity and quality of the collected data depend heavily on the precise and semantical correct representation of their metadata. In various research organizations, which are planning and coordinating studies, the required metadata are specified differently, depending on many conditions, e.g., on the used study management software. The latter does not always meet the needs of a particular research organization, e.g., with respect to the relevant metadata attributes and structuring possibilities. Methods: The objective of the research, set forth in this paper, is the development of a new approach for ontology-based representation and management of metadata. The basic features of this approach are demonstrated by the software tool OntoStudyEdit (OSE). The OSE is designed and developed according to the three ontology method. This method for developing software is based on the interactions of three different kinds of ontologies: a task ontology, a domain ontology and a top-level ontology. Results: The OSE can be easily adapted to different requirements, and it supports an ontologically founded representation and efficient management of metadata. The metadata specifications can by imported from various sources; they can be edited with the OSE, and they can be exported in/to several formats, which are used, e.g., by different study management software. Conclusions: Advantages of this approach are the adaptability of the OSE by integrating suitable domain ontologies, the ontological specification of mappings between the import/export formats and the DO, the specification of the study metadata in a uniform manner and its reuse in different research projects, and an intuitive data entry for non-expert users.