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There has been multiple advances in the management of acute respiratory distress syndrome, but the temporal trends in acute respiratory distress syndrome–related mortality are not well known. This study aimed to investigate the trends in mortality in acute respiratory distress syndrome patients over time and to explore the roles of daily fluid balance and ventilation variables in those patients.Secondary analysis of randomized controlled trials conducted by the Acute Respiratory Distress Syndrome Network from 1996 to 2013.Multicenter study involving Acute Respiratory Distress Syndrome Network trials.Patients with acute respiratory distress syndrome.None.Individual patient data from 5,159 acute respiratory distress syndrome patients (excluding the Late Steroid Rescue Study trial) were enrolled in this study. The crude mortality rate decreased from 35.4% (95% CI, 29.9–40.8%) in 1996 to 28.3% (95% CI, 22.0–34.7%) in 2013. By adjusting for the baseline Acute Physiology and Chronic Health Evaluation III, age, ICU type, and admission resource, patients enrolled from 2005 to 2010 (odds ratio, 0.61; 95% CI, 0.50–0.74) and those enrolled after 2010 (odds ratio, 0.73; 95% CI, 0.58–0.92) were associated with lower risk of death as compared to those enrolled before 2000. The effect of year on mortality decline disappeared after adjustment for daily fluid balance, positive end-expiratory pressure, tidal volume, and plateau pressure. There were significant trends of declines in daily fluid balance, tidal volume, and plateau pressure and an increase in positive end-expiratory pressure over the 17 years.Our study shows an improvement in the acute respiratory distress syndrome-related mortality rate in the critically ill patients enrolled in the Acute Respiratory Distress Syndrome Network trials. The effect was probably mediated via decreased tidal volume, plateau pressure, and daily fluid balance and increased positive end-expiratory pressure.