OBJECTIVES: The emergency department is an important venue for initial sepsis recognition and care. We sought to determine contemporary estimates of the epidemiology of U.S. emergency department visits for sepsis. DESIGN: Analysis of data from the National Hospital Ambulatory Medical Care Survey. SETTING: U.S. emergency department visits, 2009-2011. PATIENTS: Adult (age, ≥ 18 yr) emergency department sepsis patients. We defined serious infection as an emergency department diagnosis of a serious infection or a triage temperature greater than 38°C or less than 36°C. We defined three emergency department sepsis classifications: 1) original emergency department sepsis-serious infection plus emergency department diagnosis of organ dysfunction, endotracheal intubation, or systolic blood pressure less than or equal to 90 mm Hg or explicit sepsis emergency department diagnoses; 2) quick Sequential Organ Failure Assessment emergency department sepsis-serious infection plus presence of at least two "quick" Sequential Organ Failure Assessment criteria (Glasgow Coma Scale ≤ 14, respiratory rate ≥ 22 breaths/min, or systolic blood pressure ≤ 100 mm Hg); and 3) revised emergency department sepsis-original or quick Sequential Organ Failure Assessment emergency department sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used survey design and weighting variables to produce national estimates of annual adult emergency department visits using updated sepsis classifications. Over 2009-2011, there were 103,257,516 annual adult emergency department visits. The estimated number of emergency department sepsis visits were as follows: 1) original emergency department sepsis 665,319 (0.64%; 95% CI, 0.57-0.73); 2) quick Sequential Organ Failure Assessment emergency department sepsis 318,832 (0.31%; 95% CI, 0.26-0.37); and 3) revised emergency department sepsis 847,868 (0.82%; 95% CI, 0.74-0.91). CONCLUSIONS: Sepsis continues to present a major burden to U.S. emergency departments, affecting up to nearly 850,000 emergency department visits annually. Updated sepsis classifications may impact national estimates of emergency department sepsis epidemiology.