Few studies have investigated non-invasive positive pressure ventilation (NPPV) in acute respiratory distress syndrome (ARDS). The aim of this controlled cohort study was to determine the efficacy of NPPV in ARDS. Two hundred and eighty-seven patients were monitored in the respiratory intensive care unit over two years. Twenty-two subjects met the American-European consensus criteria for ARDS and were included in the study. Patients were prospectively allocated into standard therapy group and NPPV group. Indications for invasive mechanical ventilation were determined before study commencement. Invasive ventilation was applied to those needing intubation. Those in the NPPV group showing no indications for urgent intubation received NPPV in addition to standard medical therapy. Subjects with indications for intubation were intubated. Primary outcome was intubation rate; secondary outcome was hospital mortality. Seventeen patients were males, 18 (90%) patients were treated for pulmonary ARDS. Mean age was 45.2 years; mean PaO2/FiO(2) was 106.6. The need for intubation emerged for eight patients in the standard therapy group. Seven patients in the NPPV group received NPPV, and three patients in this group needed immediate intubation. NPPV was successful in 4 (57%) patients and the other three required intubation for high PEEP or NPPV intolerance. Mean duration of NPPV was 58.3 hours. There was no difference in Acute Physiology Assessment and Chronic Health Evaluation (APACHE) II scores and initial PaO2/FiO(2) values between successful and unsuccessful NPPV groups; but the difference between PaO2/FiO(2) ratios at 24 hours between these groups was statistically significant (193.0 and 93.3, respectively; p=0.003). While using NPPV in ARDS patients, if improvement is not seen in the first day, invasive mechanical ventilation should be implemented immediately.