Hospital information system, as an integrated system consists of complex, diverse, and heterogeneous information systems, which supports all clinical, administrative, and financial activities of patients,therefore, it faces interoperability problems, which is a critical feature of data sharing and integration. In this regard, a reference architecture will be presented for the integration of different systems in the hospital which comprises system, information and software architecture. This architecture emphasizes interoperability with eight layers of user interface and application, services, data collection and storage, integration, external application systems, communication and information infrastructure, management, and security/privacy, based on service orientation. It will be evaluated by ATAM method, based on ten scenarios. It shows the presented architecture will satisfy all functional and non-functional requirements such as interoperability between different information systems, reduction of information redundancy and development cost and time, scalability and accessibility.