The purpose of this investigation was to determine the predictive value of the ventilation index (VI) in children with acute respiratory distress syndrome (ARDS). We performed a 10-year retrospective chart review of children who were admitted to the Pediatric Intensive Care Unit with a diagnosis of ARDS. Acute respiratory distress syndrome was defined as acute onset of diffuse, bilateral pulmonary infiltrates of noncardiac origin, and severe hypoxemia, defined as the ratio of the arterial partial pressure of oxygen to the fraction of inspired oxygen of <200 and a positive end expiratory pressure of 6 cmH2O or greater. Records of daily arterial blood gas results and ventilator settings were reviewed, and the ventilation index (VI=partial pressure of arterial CO2 x peak airway pressure x respiratory rate/1,000) was calculated each time the measurements were made. These values were correlated with outcome (survival or nonsurvival). The VI was not different at the time of diagnosis of ARDS in the patients who lived, compared with those who subsequently died. However, by 3 to 5 days after study entry, the VI of nonsurvivors was significantly higher than for survivors (P < 0.05). The VI for survivors remained between 30 and 35 throughout the study period, whereas the VI of nonsurvivors continued to increase with time. A VI of >65 predicted death with a specificity and positive predictive value of >90% on days 3 through 9. We conclude that the VI provides a reliable prognostic marker in children with ARDS, and its increase above 65 indicates a need for orderly intervention with alternative modalities of care.