iLA Activve is a new minimally invasive device for extracorporeal CO2 removal (ECCO2-R) using a miniaturized pump, a special gas exchange membrane, and a double-lumen cannula. We retrospectively analyzed our experiences in 12 patients with hypercapnic respiratory failure undergoing ECCO2-R. Indication for ECCO2-R was hypercapnia due to terminal lung failure during bridging to lung transplantation, pneumonia, and chronic obstructive lung disease or asthma. The median duration of ECCO2-R was 8 days (range 2–30). Seven patients were successfully weaned and five died. Patients with primarily hypoxic lung failure were significantly longer ventilated before ECCO2-R and had a higher mortality rate. Complications were retroperitoneal hematoma after cannulation in one patient and repeated system changes because of clotting in two patients. We observed effective CO2 removal in all patients, with significant reduction in ventilation pressures and minute volumes at median blood flow rates of 1.2–1.4 L/min. The iLA Activve system using venous double-lumen cannulas proved to be an effective method for ECCO2-R. Invasiveness of ventilation could be reduced. Additional severe impairment of oxygenation and prolonged mechanical ventilation before ECCO2-R are factors of adverse prognosis. The use of ECCO2-R should be thoroughly reconsidered in these cases.