In actuality, it is difficult to obtain an early prognostic stratification for patients with acute respiratory failure treated with noninvasive ventilation (NIV). We tested whether an early evaluation through a predictive scoring system could identify subjects at risk of in-hospital mortality or NIV failure. This was a retrospective study, which included all the subjects with acute respiratory failure who required NIV admitted to an emergency department-high-dependence observation unit between January 2014 and December 2017. The HACOR (heart rate, acidosis [by using pH], consciousness [by using the Glasgow coma scale], oxygenation [by using [Formula: see text]/[Formula: see text]], respiratory rate) score was calculated before the NIV initiation (T0) and after 1 h (T1) and 24 h (T24) of treatment. The primary outcomes were in-hospital mortality and NIV failure, defined as the need for invasive ventilation. The study population included 644 subjects, 463 with hypercapnic respiratory failure and an overall in-hospital mortality of 23%. Thirty-six percent of all the subjects had NIV as the "ceiling" treatment. At all the evaluations, nonsurvivors had a higher mean ± SD HACOR score than did the survivors (T0, 8.2 ± 4.9 vs 6.1 ± 4.0; T1, 6.6 ± 4.8 vs 3.8 ± 3.4; T24, 5.3 ± 4.5 vs 2.0 ± 2.3 [all P < .001]). These data were confirmed after the exclusion of the subjects who underwent NIV as the ceiling treatment (T0, 8.2 ± 4.9 vs 6.1 ± 4.0 [P = .002]; T1, 6.6 ± 4.8 vs 3.8 ± 3.4; T24, 5.3 ± 4.5 vs 2.0 ± 3.2 [all P < .001]). At T24, an HACOR score > 5 (Relative Risk [RR] 2.39, 95% CI 1.60-3.56) was associated with an increased mortality rate, independent of age and the Sequential Organ Failure Assessment score. Among the subjects treated with NIV for acute respiratory failure, the HACOR score seemed to be a useful tool to identify those at risk of in-hospital mortality.