Heart failure (HF) with normal ejection fraction (EF) is an increasingly common presentation of acute decompensated HF. Differences between patients with HF and truly normal EF and those with mildly impaired EF have not been described. The Acute Decompensated Heart Failure Registry (ADHERE) contains information on >100,000 HF hospitalizations and may provide insight into this distinction. The ADHERE database was used to investigate differences between patients hospitalized with HF and severely (<25%), moderately (25% to 40%), and mildly (40% to 55%) decreased EF and those with normal EF (> or =55%). The group with normal EF was 69% women with a mean age of 74 years (p <0.0001 vs all other groups). Coronary artery disease was less frequent in the normal EF group, and hypertension played a larger role. Patients with EF > or =55% had increased pulse pressure, suggesting a role for arterial stiffening. Treatment differed by EF. Creatinine increased > or =0.5 mg/dl more often in the group with HF and normal EF than in the group with HF and severely decreased EF. In-hospital mortality and length of stay in the intensive care unit varied inversely with EF; overall length of stay was similar. In conclusion, patients with HF and normal EF are more likely to be women, have a history of high pulse pressure hypertension, less coronary artery disease, and a lower risk of inpatient death but a higher likelihood of deterioration in renal function during hospitalization. These observations may be important considerations in the design of future clinical trials.