Aim: Viral causes of acute respiratory distress syndrome (ARDS) are mostly limited to influenza A; however, adenovirus has been emerging as a cause of fulminant ARDS with a high mortality rate and no consensus on its management. Here we present a series of five patients with confirmed adenovirus infection treated for ARDS at our quaternary referral institution. Materials and methods: All patients were above 18 years old, had confirmed adenovirus infection, and were treated for acute hypoxic respiratory failure requiring mechanical ventilation in our medical intensive care unit (MICU). Demographic and clinical data were collected and analyzed. Results: Among these patients, the median age was 28 years, median BMI 28 kg/m², median sequential organ failure assessment (SOFA) score 9, and median acute physiology and chronic health evaluation (APACHE) III score 74. All patients received lung-protective mechanical ventilation with high positive end-expiratory pressure and low plateau pressures. Three patients developed severe ARDS, two received prone position ventilation, and one was placed on extracorporeal membrane oxygenation. The median duration of mechanical ventilation, MICU length of stay, and hospital length of stay were 24, 19, and 27 days, respectively. One out of five patients died in our study. Conclusion: The mortality rate for adenovirus-associated pneumonia in the literature is estimated to be 40% in those requiring mechanical ventilation. The lower mortality at our institution could be attributed to the use of standardized protocols, which include low tidal volume ventilation, early use of neuromuscular blockade, targeting low plateau pressures, conservative fluid management, and comfort and familiarity with the use of adjunctive and rescue therapies. We recommend testing for adenovirus as part of a routine respiratory viral panel in ARDS patients, and if tested positive, transfer to tertiary or quaternary centers with the experience and rescue modalities needed to manage complicated ARDS patients.