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Severe acute respiratory distress syndrome (ARDS) has a high mortality, and there is limited knowledge about management of severe ARDS refractory to standard therapy. Early evidence suggests that therapeutic hypothermia (TH) could be a viable treatment for acute respiratory failure. We present 2 cases where TH was successfully used to manage refractory ARDS on extracorporeal membrane oxygenation (ECMO) and a review of the literature around TH and acute respiratory failure.We present 2 cases of ARDS secondary to H1N1 influenza and human metapneumovirus. Both patients were treated with the current evidence-based therapy for ARDS. Venovenous ECMO was used in both patients for refractory hypoxemia. Therapeutic hypothermia was applied for 24 hours with improved oxygenation. We did a review of the literature summarizing 38 patients in 10 publications where TH was successfully utilized in the treatment of acute respiratory failure.Therapeutic hypothermia may be a viable salvage therapy for ARDS refractory to the current evidence-based therapy but needs further evaluation.