Objectives: One of the tasks of information management is systematic planning of a Hospital Information System (HIS). However, the description and the analysis of the current state of a HIS typically create high costs and are not well supported. The aim of this paper is therefore to report about the specification of a reference model for the domain layer of a Hospital Information System. Methods: We developed a reference model for the domain layer of a Hospital Information System based on the requirements index for information processing in hospitals for describing the enterprise functions, and based on the object types from the Health Level 7 Reference Information Model (HL7-RIM) for describing the entity types. Result: The developed reference model is a comprehensive hierarchic model of the enterprise functions of hospital information systems. The central enterprise function “patient treatment” for example is described with 35 enterprise functions and 38 entity types on a three-level hierarchy. Discussion: Reference models provide a kind of modelling patterns that can easily be used and adapted to a respective Information System. The availability of reference models should therefore provide a highly valuable contribution to keep the costs for modelling Hospital Information Systems low. We will start to evaluate the reference model by using it in the description of the information systems of a University Clinic of the Tiroler Landeskrankenanstalten GmbH (TILAK), Austria. If this pre-test is positive, it is planned to extend the use of the reference model to the overall Hospital Information System of the TILAK.