Abstract Background: Acute respiratory distress syndrome is a clinical syndrome characterized by a refractory hypoxemia due to an inflammatory and high permeability pulmonary edema secondary to direct or indirect lung insult (pulmonary and extrapulmonary form). These two categories of ARDS patients are different regarding the respiratory mechanics, lung recruitment, gas exchange, and positive end-expiratory pressure response. Aim of Study: The aim of this work was to compare the clinical characteristics and outcomes between the two major ARDS subtypes; pulmonary and extrapulmonary. Patients and Methods: A prospective study was conducted during the period from July 2014 to January 2016 in Intensive Care Unit, El-Hussein University Hospital. It included 60 patients diagnosed as ARDS. They were subclassified into pulmonary and extrapulmonary ARDS groups according to the cause of lung injury. Both groups were compared regarding the clinical features, response to treatment and clinical outcome. Results: Patients with extrapulmonary ARDS developed more deteriorated liver and renal functions and arterial blood gases with a better response to elevated levels of PEEP and vasopressors with a mortality rate of 75%. In patients with pulmonary ARDS, mild organs dysfunction were developed with a better response to low levels of PEEP and a mortality rate of 25%. Conclusion: Subdivision of ARDS into pulmonary and extrapulmonary categories has worthy effect on both treatment and clinical outcome. Additionally, they are different in the degree of organ dysfunction and severity of clinical pictures. Recommendation: Proper assessment of patients with ARDS at admission to put them within a major category whether pulmonary or extrapulmonary ARDS. This simple classification will help physician to decide on treatment and to predict prognosis.