Purpose: Lung protective ventilation is recommended in patients with acute respiratory distress syndrome (ARDS) needing mechanical ventilation. This can however be associated with hypercapnia and respiratory acidosis, such that extracorporeal CO2 removal (ECCO2 R) can be applied. The aim of this study was to derive optimal operating parameters for the ECCO2 R Abylcap (R) system (Bellco, Italy). Methods: We included 4 ARDS patients with a partial arterial oxygen tension over the fraction of inspired oxygen (PaO2 /FiO(2)) lower than 150 mmHg, receiving lung-protective ventilation and treated with the Abylcap (R) via a double lumen 13.5-Fr dialysis catheter in the femoral vein. Every 24 hours during 5 consecutive days, blood was sampled at the Abylcap (R) inlet and outlet for different blood flows (Q(B) : 200-300-400 mL/min) with 100% O-2 gas flow (Q(G)) of 7 L/min, and for different Q(G) (Q(G) : 0.5-1-1.5-3-6-8 L/min) with Q(B) 400 mL/min. CO2 and O-2 transfer remained constant over 5 days for a fixed Q(B). Results: We found that, for a fixed Q(G) of 7 L/min, CO2 transfer linearly and significantly increased with Q(B) (i.e. from 58 +/- 8 to 98 +/- 16 mL/min for Q(B) 200 to 400 mL/min). For a fixed Q(B) of 400 mL/min, CO2 transfer non-linearly increased with Q(G) (i.e. from 39 +/- 9 to 98 +/- 16 mL/min for Q(G) 0.5 to 8 L/min) reaching a plateau at Q(G) of 6 L/min. Conclusions: Hence, when using the Abylcap (R) ECCO2 R in the treatment of ARDS patients the O-2 flow should be at least 6 L/min while Q(B) should be set at its maximum.