Three hundred fifteen consecutive patients with acute respiratory failure (ARF) were treated to the same end point. Based on blood gas determination, positive end-expiratory pressure (PEEP) was added in incremental steps to either maintain or reduce intrapulmonary shunt to 15%. Mean optimal PEEP level was 15.3 ± 9.2 cm H2O. Duration of PEEP was 4.0 days, and mechanical ventilatory support was necessary 2.2 days. Overall mortality was 28% (88/315); 1 % (3/315) died of refractory respiratory failure. The final optimal PEEP level did not correlate with length of interventions, fluid requirements, mortality, or final attained shunt value. Goal-directed therapy was not only effective in achieving a low mortality from acute respiratory failure, but permits a valid comparison between patients of the severity of respiratory dysfunction. That comparison is based on magnitude and length of interventions required to attain preselected therapeutic end points.