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Background Right ventricular (RV) failure is a common complication in moderate-to-severe acute respiratory distress syndrome (ARDS). RV failure is exacerbated by hypercapnic acidosis and overdistension induced by mechanical ventilation. Veno-venous extracorporeal CO2 removal (ECCO2R) might allow ultraprotective ventilation with lower tidal volume (VT) and plateau pressure (Pplat). This study investigated whether ECCO2R therapy could affect RV function. Methods This was a quasi-experimental prospective observational pilot study performed in a French medical ICU. Patients with moderate-to-severe ARDS with PaO2/FiO2 ratio between 80 and 150 mmHg were enrolled. An ultraprotective ventilation strategy was used with VT at 4 mL/kg of predicted body weight during the 24 h following the start of a low-flow ECCO2R device. RV function was assessed by transthoracic echocardiography (TTE) during the study protocol. Results The efficacy of ECCO2R facilitated an ultraprotective strategy in all 18 patients included. We observed a significant improvement in RV systolic function parameters. Tricuspid annular plane systolic excursion (TAPSE) increased significantly under ultraprotective ventilation compared to baseline (from 22.8 to 25.4 mm; p S’ wave) also increased after the 1-day protocol (from 13.8 m/s to 15.1 m/s; p p = 0.05). There were no significant differences in the values of systolic pulmonary arterial pressure (sPAP) and RV preload. Conclusion Low-flow ECCO2R facilitates an ultraprotective ventilation strategy thatwould improve RV function in moderate-to-severe ARDS patients. Improvement in RV contractility appears to be mainly due to a decrease in intrathoracic pressure allowed by ultraprotective ventilation, rather than a reduction of PaCO2.