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We identified risk factors for noninvasive ventilation (NIV) failure in patients with acute cardiogenic pulmonary edema (ACPE).We conducted an observational cohort study over a 3-year period in a 28-bed emergency intensive care unit (EICU) and prospectively included all consecutive patients in whom NIV was attempted as initial ventilatory support for ACPE. The primary outcome variables were NIV failure rate and risk factors for NIV failure.Among the 118 patients in the study, NIV failed for 44 (37.3%) patients. Risk factors for NIV failure were Killip class IV (odds ratio [OR], 28.56; 95% confidence interval [CI], 2.17–375.73; p = 0.011), left ventricular ejection fraction (LVEF) < 30% (OR, 9.54; 95% CI, 1.01–90.55; p = 0.050) and B-type natriuretic peptide (BNP) ≥ 3350 pg/mL (OR, 39.63; 95% CI, 3.92–400.79; p = 0.002) at baseline, and fluid balance ≥ 400 mL within 24 h after ACPE (OR, 13.19; 95% CI, 1.18–147.70; p = 0.036).NIV failure occurred in 37.3% of ACPE patients in a real-world EICU. When patients had Killip class IV, a lower LVEF, a higher BNP, and a more positive fluid balance within 24 h after ACPE, the risk of failure was higher.NCT02653365.The rate of NIV failure reached 37.3% in patients with ACPE in a real-world EICU.Killip class IV, LVEF < 30%, BNP ≥ 3,350 pg/mL, and fluid balance ≥ 400 mL within 24 h were risk factors for NIV failure.Delayed intubation may be associated with decreased survival in patients with ACPE.