We retrospectively reviewed the medical records of 11 patients supported with a veno-venous low-flow extracorporeal carbon dioxide (CO2) removal (ECCO2R) device featuring a large gas exchange surface membrane lung (ML) (i.e., 1.8 m2). Seven patients suffered from exacerbation of a chronic pulmonary disease, while four subjects were affected by acute respiratory distress syndrome (ARDS). Twenty-four hours of ECCO2R treatment reduced arterial PCO2 from 63 ± 12 to 54 ± 11 mm Hg (p < 0.01), increased arterial pH from 7.29 ± 0.07 to 7.39 ± 0.06 (p < 0.01), and decreased respiratory rate from 32 ± 10 to 21 ± 8 bpm (p < 0.05). Extracorporeal blood flow and CO2 removal were 333 ± 37 and 94 ± 18 ml/min, respectively. The median duration of ECCO2R treatment was 7 days (6.5–9.5). All four ARDS patients were invasively ventilated at the time of treatment start, no one was extubated and they all died. Among the seven patients with exacerbation of chronic pulmonary diseases, four were managed with noninvasive ventilation at ECCO2R institution, while three were extubated after starting the extracorporeal treatment. No one of these seven patients was intubated or re-intubated after ECCO2R institution and five (71%) survived to hospital discharge. A low-flow ECCO2R device with a large surface ML removes a relevant amount of CO2 resulting in a decreased arterial PCO2, an increased arterial pH, and in a reduced ventilatory load.