In this paper we assess the value of electronic health care information exchange and interoperability (HIEI) between providers (hospitals and medical group practices) and independent laboratories, radiology centers, pharmacies, payers, public health departments, and other providers. We have created an HIEI taxonomy and combined published evidence with expert opinion in a cost-benefit model. Fully standardized HIEI could yield a net value of dollar 77.8 billion per year once fully implemented. Nonstandardized HIEI offers smaller positive financial returns. The clinical impact of HIEI for which quantitative estimates cannot yet be made would likely add further value. A compelling business case exists for national implementation of fully standardized HIEI.