For acutely ill patients, health care services are available in many different settings, including hospital-based emergency departments (EDs), retail clinics, federally qualified health centers, and outpatient clinics. Certain conditions are the sole domain of particular settings: stabilization of critically ill patients can typically only be provided in EDs. By contrast, many conditions that do not require hospital resources, such as advanced radiography, admission, and same-day consultation can often be managed in clinic settings. Because clinics are generally not open nights, and often not on weekends or holidays, the ED remains the only option for face-to-face medical care during these times. For patients who can be managed in either setting, there are many open research questions about which is the best setting, because these venues differ in terms of access, costs of care, and potentially, quality. Consideration of these patients must be risk-adjusted, as patients may self-select a venue for care based upon perceived acuity. We present a research agenda for acute, unscheduled care in the United States developed in conjunction with an Agency for Healthcare Research and Quality-funded conference hosted by the American College of Emergency Physicians in October 2009, titled "Improving the Quality and Efficiency of Emergency Care Across the Continuum: A Systems Approach." Given the possible increase in ED utilization over the next several years as more people become insured, understanding differences in cost, quality, and access for conditions that may be treated in EDs or clinic settings will be vital in guiding national health policy.