Healthcare is an increasingly collaborative enterprise involving many individuals and organizations that coordinate their efforts toward promoting quality and efficient delivery of healthcare through the use of interoperable healthcare information systems. This paper presents a mediator-based approach for achieving data and service interoperability among disparate and geographically dispersed healthcare information systems. The proposed system architecture enables decoupling of the client applications and the server-side implementations while it ensures security in all transactions. It is a distributed system architecture based on the agent-oriented paradigm for communication and life cycle management while interactions are described according to the workflow metaphor. Thus robustness, high flexibility and fault tolerance are provided in an environment as dynamic and heterogeneous as healthcare.