BACKGROUND: Studies of ventilation strategies that included higher PEEP in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) have yielded conflicting results. OBJECTIVE: To determine whether higher PEEP during volume-limited and pressure-limited ventilation is associated with 28-day mortality or barotrauma rates in patients with ALI/ARDS. METHODS: We searched MEDLINE, CENTRAL, EMBASE, CINAHL, Web of Science, and the bibliographies of retrieved papers to identify randomized controlled trials that compared higher and lower PEEP in adult patients with ALI/ARDS who were already receiving volume-limited or pressure-limited ventilation. Two of us independently abstracted study-level data, including study design, patient characteristics, study methods, intervention, and main results. We pooled the study-level data with a random-effects model, unless heterogeneity was low (I2 < 50%), in which case we used a fixed-effects model. The primary outcome was 28-day mortality. RESULTS: Four randomized trials (2,360 participants) were evaluated. Higher PEEP had a nonsignificant trend toward lower 28-day mortality (pooled relative risk 0.90, 95% CI 0.79‐1.02). There was no difference in barotrauma between the 2 groups (pooled relative risk 1.17, 95% CI 0.90‐1.52). Two studies reported an adjusted hospital death rate, and the pooled results of sensitivity analysis with those adjusted rates were identical to those of the unadjusted analysis. CONCLUSIONS: In 4 recent studies that used volume-limited or pressure-limited ventilation in ALI/ARDS patients, higher PEEP was not associated with significantly different short-term mortality or barotrauma. This study does not support the routine use of higher PEEP in patients with ALI/ARDS.