OBJECTIVE: Diffuse alveolar damage (DAD) is considered the histologic hallmark of ARDS although DAD is absent in approximately half of patients with ARDS. The clinical implications of having the syndrome of ARDS with DAD vs other histologic patterns is unknown. To address this question, we conducted a meta-analysis of lung biopsy series for patients with ARDS. METHODS: Studies were identified using MEDLINE, EMBASE, Cochrane Register of Controlled Trials, LILACS, and citation review from January 1, 1967, to September 1, 2015. Studies were included if they included all of the following: open lung biopsies (OLB) performed after ARDS diagnosis; a clear definition of ARDS and DAD; histologic results of the OLB indicated the presence or absence of DAD; and mortality reported for the DAD and non-DAD groups. We excluded studies conducted solely on a specific histology subgroup (eg, DAD) and studies with fewer than 5 patients. Two authors independently selected studies for inclusion, and there were no language restrictions. RESULTS: Of 8 included studies, 4 were high-quality (n = 228) and 4 were middle-quality trials (n = 122). The meta proportion of DAD between all the groups was 0.45 (95% CI, 0.35-0.56; Q test, 21.1; I2, 66.8%; P <= .01). The pooled OR for mortality in ARDS with DAD compared with ARDS without DAD was 1.81 (95% CI, 1.14-2.80; Q test, 8.8; I-2, 20.2%; P = .269). Age, sex, and days elapsed between ARDS diagnosis and OLB as well as sequential organ failure assessment score and PaO2/FIO2 ratio on the day of OLB did not differ between DAD and non-DAD groups. CONCLUSIONS: This meta-analysis demonstrated that ARDS with DAD is associated with higher mortality than ARDS without DAD.