Inclusion Criteria:  Age > 18 years On invasive mechanical ventilation for ≤ 96 hours Presence of all of the following conditions for ≤ 24 hours: 100 < PaO2/FiO2 ≤ 200 after 12 hours of "standardized ventilation" with PEEP ≥ 5; compliance of the respiratory system ≤ 0.5 ml/cmH2O per kg PBW; bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules; respiratory failure not fully explained by cardiac failure or fluid overload  Exclusion Criteria:  Pregnancy ARDS with PaO2/FiO2<100 or PaO2/FiO2>200 under standardized ventilation with PEEP ≥ 5 cmH2O Expected duration of mechanical ventilation < 48 hours Severe COPD Chronic respiratory insufficiency with home ventilation or oxygen therapy Currently receiving ECMO therapy Acute brain injury Severe liver insufficiency (Child-Pugh scores >7) or fulminant hepatic failure Heparin-induced thrombocytopenia Contraindication for systemic anticoagulation Platelet count <50,000/mm3 Prothrombin time-international normalized ratio (INR) >1.5 Patient moribund, decision to limit therapeutic interventions End-stage disease Unable to provide vascular access for ECCO2-R Acute coronary syndrome Actual body weight exceeding 1 kg per centimeter of height Burns > 40% total body surface Bone marrow transplantation within the last 1 year