Data and financial models based on an operational health information exchange suggest that health care delivery costs can be reduced by making clinical data available at the time of care in urban emergency departments. Reductions are the result of decreases in laboratory and radiographic tests, fewer admissions for observation, and lower overall emergency department costs. The likelihood of reducing these costs depends on the extent to which clinicians alter their workflow and take into account information available through the exchange from other institutions prior to initiating a treatment plan. Far greater savings can be realized in theory by identifying individuals presenting to emergency departments whose acute and long-term care needs are more suitably addressed at lower costs in ambulatory settings or medical homes. These alternative ambulatory settings can more effectively address the chronic care needs of those who receive most of their care in emergency departments. To support a shift from emergency room care to clinic care, health care information available through the health information exchange must be made available in both emergency department and ambulatory care settings. If practice workflow and patient behavior can be changed, a more effective and efficient care delivery system will be made possible through the secure exchange of clinical information across regional settings. These projections support the case for the financial viability of regional health information exchanges and motivate participation of hospitals and ambulatory care organizations-particularly in urban settings.