In the setting of acute decompensated heart failure (HF), relations among the etiology of HF, left ventricular systolic function, and outcomes are unclear. The aim of this study was to investigate the association of HF etiology with outcomes in patients with acute decompensated HF with a preserved or reduced ejection fraction (EF). Of the 4,842 patients enrolled in the Acute Decompensated Heart Failure Syndromes registry, 3,810 patients (1,601 with a preserved EF and 2,209 with a reduced EF) who had a hypertensive, ischemic, valvular, or idiopathic dilated etiology of HF were investigated to assess the association of etiology with a composite end point (all-cause mortality and readmission for HF). The median follow-up period after admission was 502 (381 to 759) days. The composite end point was reached in 44.6% and 41.7% of the preserved and reduced EF groups, respectively. After adjustment for multiple co-morbidities, the risk of the composite end point was comparable among hypertensive, ischemic, and valvular etiologies in the preserved EF group. In contrast, in the reduced EF group, ischemic etiology was associated with a tendency toward greater risk of the composite end point than hypertensive etiology (but this difference was not significant), whereas valvular etiology was associated with a significantly greater risk of the composite end point relative to hypertensive or idiopathic dilated etiology. In conclusion, this study demonstrated that taking the etiology of HF into account may help to reduce the heterogeneity of acute decompensated HF and assist in identifying patients at risk of adverse outcomes, especially among patients with reduced EF.