Objective: To present the successful experiences of an integrated, collaborative, distributed, large-scale enterprise healthcare information system over a wired and wireless infrastructure in National Taiwan University Hospital (NTUH). In order to smoothly and sequentially transfer from the complex relations among the old (legacy) systems to the new-generation enterprise healthcare information system, we adopted the multitier framework based on service-oriented architecture to integrate the heterogeneous systems as well as to interoperate among many other components and multiple databases. We also present mechanisms of a logical layer reusability approach and data (message) exchange flow via Health Level 7 (HL7) middleware, DICOM standard, and the Integrating the Healthcare Enterprise workflow. The architecture and protocols of the NTUH enterprise healthcare information system, especially in the Inpatient Information System (IIS), are discussed in detail. Implementation: The NTUH Inpatient Healthcare Information System is designed and deployed on service-oriented architecture middleware frameworks. The mechanisms of integration as well as interoperability among the components and the multiple databases apply the HL7 standards for data exchanges, which arc embedded in XML formats, and Microsoft .NET Web services to integrate heterogeneous platforms. Measurements: The preliminary performance of the current operation IFS is evaluated and analyzed to verify the efficiency and effectiveness of the designed architecture; it shows reliability and robustness in the highly demanding traffic environment of NTUH. Conclusions: The newly developed NTUH IIS provides an open and flexible environment not only to share medical information easily among other branch hospitals, but also to reduce the cost of maintenance. The HL7 message standard is widely adopted to cover all data exchanges in the system. All services are independent modules that enable the system to be deployed and configured to the highest degree flexibility. Furthermore, we can conclude that the multitier Inpatient Healthcare Information System has been designed successfully and in a collaborative manner, based on the index of performance evaluations, central processing unit, and memory utilizations.