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To determine the outcome from the use of noninvasive positive pressure ventilation (NPPV) in “do-not-intubate” (DNI) patients in acute respiratory failure.Prospective observational study.University-affiliated large medical center.All patients with DNI status who received NPPV for a 1-yr period.None.Demographic, physiologic, and laboratory data were collected before initiation, 2 hrs after initiation, and each morning and evening for as long as NPPV was provided. Data were recorded on 137 episodes of acute respiratory failure in 131 DNI patients. Hospital mortality rate was 37.5% in 24 patients with an exacerbation of chronic obstructive pulmonary disease (COPD), 39% in 28 patients with acute cardiogenic pulmonary edema, 68% in nine patients with non-COPD hypercapnic ventilatory failure, 77% in 13 postextubation respiratory failure patients, and 86% in 57 patients with hypoxemic respiratory failure. Advanced cancer was present in 40 patients and was associated with increased risk of death (85% mortality rate, p = .002). A score based on the Simplified Acute Physiology Score (SAPS) II and serum albumin level calculated before NPPV was predictive of hospital outcome.NPPV is successful in reversing acute respiratory failure and preventing hospital mortality in DNI patients with COPD and cardiogenic pulmonary edema but not in patients with postextubation failure, hypoxemic respiratory failure, or end-stage cancer. An easy-to-calculate score combining SAPS II and serum albumin level is a good prediction of outcome in DNI patients receiving NPPV.