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We examined whether patients with acute respiratory distress syndrome (ARDS) lacking risk factors are enrolled in therapeutic trials and assessed their clinical characteristics and outcomes.We performed a secondary analysis of patient-level data pooled from the ARMA, ALVEOLI, FACTT, ALTA and EDEN ARDSNet randomized controlled trials obtained from the Biologic Specimen and Data Repository Information Coordinating Center of the National Heart, Lung and Blood Institute. We compared baseline characteristics and clinical outcomes (before and after adjustment using Poisson regression model) of ARDS patients with versus without risk factors.Of 3733 patients with ARDS, 81 (2.2%) did not have an identifiable risk factor. Patients without risk factors were younger, had lower baseline severity of illness, were more likely to have the ARDS resolve rapidly (i.e., within 24 h) (p < 0.001) and they had more ventilator-free days (median 21; p = 0.003), more intensive care unit-free days (18; p = 0.010), and more non-pulmonary organ failure-free days (24; p < 0.001) than comparators (17, 14 and 18, respectively). Differences persisted after adjustment for potential confounders.Patients with ARDS without identifiable risk factors are enrolled in therapeutic trials and may have better outcomes, including a higher proportion of rapidly resolving ARDS, than those with risk factors.Patients with ARDS without identifiable risk factors are enrolled in therapeutic trials.Patients without risk factors may have better outcomes, including a higher proportion of rapidly resolving ARDS, than those with risk factors.Clinicians should be aware that some of the patients without risk factors may respond rapidly to standard care.