Purpose To develop and validate a scale using variables easily obtained at the bedside for prediction of failure of noninvasive ventilation (NIV) in hypoxemic patients. Methods The test cohort comprised 449 patients with hypoxemia who were receiving NIV. This cohort was used to develop a scale that considers heart rate, acidosis, consciousness, oxygenation, and respiratory rate (referred to as the HACOR scale) to predict NIV failure, defined as need for intubation after NIV intervention. The highest possible score was 25 points. To validate the scale, a separate group of 358 hypoxemic patients were enrolled in the validation cohort. Results The failure rate of NIV was 47.8 and 39.4% in the test and validation cohorts, respectively. In the test cohort, patients with NIV failure had higher HACOR scores at initiation and after 1, 12, 24, and 48 h of NIV than those with successful NIV. At 1 h of NIV the area under the receiver operating characteristic curve was 0.88, showing good predictive power for NIV failure. Using 5 points as the cutoff value, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for NIV failure were 72.6, 90.2, 87.2, 78.1, and 81.8%, respectively. These results were confirmed in the validation cohort. Moreover, the diagnostic accuracy for NIV failure exceeded 80% in subgroups classified by diagnosis, age, or disease severity and also at 1, 12, 24, and 48 h of NIV. Among patients with NIV failure with a HACOR score of >5 at 1 h of NIV, hospital mortality was lower in those who received intubation at ≤12 h of NIV than in those intubated later [58/88 (66%) vs. 138/175 (79%); p = 0.03). Conclusions The HACOR scale variables are easily obtained at the bedside. The scale appears to be an effective way of predicting NIV failure in hypoxemic patients. Early intubation in high-risk patients may reduce hospital mortality.