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Background: The addition of both noninvasive continuous positive airway pressure (n-CPAP) or noninvasive intermittent positive pressure ventilation (n-IPPV) to medical treatment has been shown to improve the outcome of patients with acute cardiogenic pulmonary edema (ACPE). Previous studies indicated a potential risk of new-onset acute myocardial infarction (AMI) associated with the use of n-IPPV. Although further studies did not confirm this observation, a few recent metaanalyses could not eliminate all the doubts at this regards because of the paucity of data available and the presence of confounding factors. This study aims to assess whether the application of n-IPPV, as opposed to n-CPAP, increases the rate of AMI in ACPE patients., Methods: Fifty-two patients with severe hypoxemia consequent to ACPE were randomized to receive n-CPAP (n = 27) or n-IPPV (n = 25) in addition to medical therapy. Patients with signs of acute coronary syndrome on hospital admission were excluded from the study. Cardiac markers, ECG, and clinical/physiologic parameters were assessed at study entry, after 30 and 60 min, and every 6 h for the first 2 days., Results: No significant difference was observed in the rate of AMI (26.9% and 16% with n-CPAP and n-IPPV, respectively, p = 0.244). Rate of intubation (p = 0.481), death (p = 0.662), and hospital stay (p = 0.529) were not different between the two groups. Both techniques were effective in improving gas exchange and vital signs in patients with ACPE., Conclusions: The AMI rate was not different with n-CPAP and n-IPPV, which resulted to be equally effective in the treatment of ACPE., Trial Registration: Clinicaltrials.gov Identifier: NCT00453947.