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The objective of the study is to determine the 28-day mortality of critically ill cancer patients with acute respiratory distress syndrome (ARDS).This is a retrospective cohort study of patients enrolled in the ARDS Network randomized controlled trials.A total of 2515 patients did not have cancer, and 116 patients had cancer. Patients with cancer were older (median, 61 vs 49 years; P < .0001), more critically ill (the median Acute Physiology and Chronic Health Evaluation III score without cancer comorbidity was 105 for the cancer group compared with 87 for those without cancer; P < 0.0001), and more likely to have pneumonia or sepsis as cause of acute lung injury (79.31% vs 62.70%; P = .0011). The overall mortality at day 28 was 25.7%. Patients with cancer had significantly higher mortality (55.2%) compared with those without cancer (24.3%) (P < .0001). The odds ratio for mortality from ARDS at 28 days for cancer patients was 2.54 (95% confidence interval [CI], 1.570-4.120). Acute Physiology and Chronic Health Evaluation III score and age were found to be significant predictors of outcome in cancer patients with odds ratio of 1.034 (95% CI, 1.007-1.062; P = .0135) and 1.075 (95% CI, 1.024-1.129, P = .0036), respectively.Cancer patients with ARDS have a significantly higher risk of death compared with those without cancer. The increased risk appeared to be mediated by increased severity of illness at presentation, as well as by age.