Extracorporeal carbon dioxide removal (ECCO2R) has been gaining interest to potentially facilitate gas transfer and equilibrate mild to moderate hypercapnic acidosis, when standard therapy with non-invasive ventilation is deemed refractory. However, concern regarding the effectiveness of low-flow CO2 removal remains. Additionally, the prospect to steadily reduce hypercapnia via low-flow ECCO2R technique is limited, especially with regional anticoagulation which potentially reduces the risk of bleeding. Therefore, an in vivo study was conducted to determine the efficacy of CO2 removal through a modified renal dialysis unit during the carbon dioxide dialysis study using systemic and regional anticoagulation.The acute study was conducted for 14?h in landrace pigs (51?3?kg). CO2 removal using a diffusion membrane oxygenator substituting the hemoconcentrator was provided for 6?h. Blood and gas (100?% O2) flows were set at 200 and 5?L/min, respectively. Anticoagulation was achieved by systemic heparinization (n?=?7) or regional trisodium citrate 4?% (n?=?7).The CO2 transfer was highest during the initial hour and ranged from 45 to 35?mL/min, achieving near eucapnic values. Regional and systemic anticoagulation were both effective in decreasing arterial pCO2 (from 8.9?1.3?kPa to 5.6?0.8?kPa and from 8.6?1.0?kPa to 6.3?0.7?kPa, p?