Subjects with heart failure (HF) and a preserved ejection fraction (EF) are heterogenous and the EF used to define this syndrome varies considerably among studies. We sought to determine if physiologic differences exist between subjects with a normal EF (>55%) or mildly decreased EF (40% to 55%). 357 consecutive Chinese patients who were healthy (n = 93) or had HF (n = 264) underwent comprehensive echocardiography, Doppler analysis, and measurement of neurohormones. Subjects with HF were stratified by EF into those with normal EF (>55%, n = 128), mildly decreased EF (40% to 55%, n = 38), or moderate to severely decreased EF (<40%, n = 100). Employing noninvasive pressure-volume analysis, estimated end-systolic and end-diastolic pressure-volume relations were calculated. Subjects with HF and an EF 40% to 55% more often had a previous myocardial infarction and diabetes than those with HF and an EF >55%. Physiologically, the cohort with a mildly decreased EF had eccentrically enlarged ventricles with evidence of remodeling (rightward shifted end-diastolic pressure-volume relation) and decreased chamber contractility (downward shifted end-systolic pressure-volume relation) most comparable to subjects with overt systolic HF. In conclusion, in subjects with HF and a preserved EF, there are distinct physiologic differences between those with a normal (>55%) and a mildly decreased (40% to 55%) EF.