Several nations and local communities are striving to achieve widespread, secure exchange of clinical data between various health care providers and public health organizations. Most of the literature on health information exchange focuses on the financial, political, and privacy aspects of these initiatives. Perhaps just as important are the technical and organizational factors that have influenced development of data exchange methods and results. One mature network in the Midwestern United States has had success in establishing consistent, secure exchange of clinical data for more than ten years. Presented here are the technical lessons learned and design decisions made from this initiative with the hope that they can be used by others striving to connect disparate clinical information systems for the improvement of health care quality and safety.