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A recent post hoc analysis suggested that driving pressure may be more important than traditional ventilatory variables in determining outcome in mechanically ventilated patients with acute respiratory distress syndrome. We conducted a systematic review and meta-analysis to summarize the risk of mortality for higher versus lower driving pressure.MEDLINE, EMBASE, PubMed, CINAHL, and Cochrane CENTRAL from inception to February 10, 2017.Studies including mechanically ventilated adult patients with acute respiratory distress syndrome, reporting driving pressure and mortality.Seven studies including five secondary analysis of previous randomized controlled trials and two observational studies (6,062 patients) were eligible for study. All studies were judged as having a low risk of bias. Median (interquartile range) driving pressure between higher and lower driving pressure groups was 15 cm H2O (14–16 cm H2O). Median (interquartile range) mortality of all included studies was 34% (32–38%).In the meta-analyses of four studies (3,252 patients), higher driving pressure was associated with a significantly higher mortality (pooled risk ratio, 1.44; 95% [CI], 1.11–1.88; I2 = 85%). A sensitivity analysis restricted to the three studies with similar driving pressure cutoffs (13–15 cm H2O) demonstrated similar results (pooled risk ratio, 1.28; 95% CI, 1.14–1.43; I2 = 0%).Our study confirmed an association between higher driving pressure and higher mortality in mechanically ventilated patients with acute respiratory distress syndrome. These findings suggest a possible range of driving pressure to be evaluated in clinical trials. Future research is needed to ascertain the benefit of ventilatory strategies targeting driving pressure in patients with acute respiratory distress syndrome.