Purpose: To compare characteristics and clinical outcomes of patients receiving airway pressure release ventilation (APRV) or biphasic positive airway pressure (BIPAP) to assist-control ventilation (A/C) as their primary mode of ventilatory support. The objective was to estimate if patients ventilated with APRV/BIPAP have a lower mortality. Methods: Secondary analysis of an observational study in 349 intensive care units from 23 countries. A total of 234 patients were included who were ventilated only with APRV/BIPAP and 1,228 patients who were ventilated only with A/C. A case-matched analysis according to a propensity score was used to make comparisons between groups. Results: In logistic regression analysis, the most important factor associated with the use of APRV/BIPAP was the country (196 of 234 patients were from German units). Patients with coma or congestive heart failure as the reason to start mechanical ventilation, pH <7.15 prior to mechanical ventilation, and patients who developed respiratory failure (SOFA score >2) after intubation with or without criteria of acute respiratory distress syndrome were less likely to be ventilated with APRV/BIPAP. In the case-matched analysis there were no differences in outcomes, including mortality in the intensive care unit, days of mechanical ventilation or weaning, rate of reintubation, length of stay in the intensive care unit or hospital, and mortality in the hospital. Conclusions: In this study, the APRV/BIPAP ventilation mode is being used widely across many causes of respiratory failure, but only in selected geographic areas. In our patient population we could not demonstrate any improvement in outcomes with APRV/BIPAP compared with assist-control ventilation.