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Objectives: To assess (1) the short-term hemodynamic, respiratory and arterial blood gas effects of NIPSV in patients with ACPE who were likely to require endotracheal intubation, (2) the initial causes of failure and (3) the side effects and the difficulties of this technique. Design: Uncontrolled, prospective clinical study. Setting: Teaching hospital intensive care unit. Patients: 26 consecutive patients with severe ACPE. Interventions: Noninvasive ventilation via a face mask, using a pressure support mode (20.5 ± 4.7 cmH2O), with an initial fractional inspired oxygen of 93.0 ± 16 % and a positive end-expiratory pressure of 3.5 ± 2.3 cmH2O. The need to intubate the patients within 48 h was considered as a criterion of failure of the procedure. Measurements and results: Clinical and biological parameters were measured at 15 and 30 minutes, 1 h and 2 h and at 1 h and 2 h, respectively. There were 5 (21 %) failures and 21 (79 %) successes. In both the success and the failure groups, clinical and blood gas parameters improved at the first measure. In the success group, within 15 min of the start of NIPSV, pulse oximetry saturation (SpO2) had increased from 84 ± 12 to 96 ± 4 % (p < 0.001), the respiratory rate (RR) had decreased from 36 ± 5.3 to 22.4 ± 4.9 breaths/min (p < 0.0001) and within 1 h the arterial oxygen tension and pH, respectively, had increased from 61 ± 14 to 270 ± 126 mmHg (p < 0.0001) and from 7.25 ± 0.11 to 7.34 ± 0.07 (p < 0.01) and the arterial carbon dioxide tension (PaCO2) had decreased from 54.2 ± 15 to 43.4 ± 6.4 mmHg (p < 0.01). There were no statistical differences between the success and failure groups for the initial clinical parameters: SpO2, RR, heart rate, mean arterial pressure. The only differences between the success and failure groups were in the PaCO2 (54.2 ± 15 vs 32 ± 2.1 mmHg, p < 0.001) and the creatine kinase (CPK) (176 ± 149 vs 1282 ± 2080 IU/l, p < 0.05); this difference in CPK activity was related to the number of patients who had an acute myocardial infarction (AMI) (4/5 in the failure group vs 2/21 in the success group, p < 0.05). All patients with AMI in the failure group died. Conclusion: Among patients in acute respiratory failure, those with severe ACPE could benefit from NIPSV if they are hypercapnic, but NIPSV should be avoided in those with AMI.