Abstract Background The Targeted Therapeutic Mild Hypercapnia After Resuscitated Cardiac Arrest (TAME) trial found similar neurological outcomes between mild hypercapnia and normocapnia in resuscitated out-of- hospital cardiac arrest (OHCA) patients. Hypercapnic acidosis can cause pulmonary vasoconstriction and aggravate right ventricular dysfunction, which is common and associated with worsened outcomes after OHCA. Purpose We investigated the effects of targeting mild hypercapnia on right ventricular function. Methods Single-centre, pre-planned and prospective sub-study. Comatose OHCA patients were randomised to targeted mild hypercapnia (PaCO2 =6.7–7.3 kPa) or targeted normocapnia (PaCO 2 =4.7- 6.0 kPa) for 24 hours. Transthoracic echocardiography was performed at baseline, during intervention and 48 hours after randomisation. Serial right heart catherisation (RHC) was performed if available. Results A total of 137 patients were randomised, 111 were evaluated with echocardiography and 52 and 59 randomised to mild hypercapnia and normocapnia, respectively. 84 patients received RHC; 41 and 43 in the hypercapnia and normocapnia-group, respectively. Overall, the median age was 64 years, 80 % were male and median time to ROSC was 22 minutes. Baseline characteristics did not differ significantly between treatments groups (p >0.05). Targeting mild hypercapnia was associated with lower tidal volumes, respiratory frequencies and respiratory acidosis (P-group < 0.05). Positive end-expiratory pressure, right atrial pressure, pulmonary vascular resistance index and pulmonary capillary wedge pressure were similar between groups (P-group > 0.05). Median time to echocardiography after randomisation was 21 (IQR 14-23) and 17 (IQR 9-22) hours in the hypercapnia and normocapnia-group, respectively. Tricuspid annular plane systolic excursion (TAPSE) was similar between treatment-groups at baseline and higher in the hypercapnia-group during the intervention with a median of 21 mm (IQR 18-23) versus 16 mm (IQR 13-21), p = 0.002. S', fractional area change (FAC) and the ratio of TAPSE to the pulmonary artery systolic pressure (PASP) were all higher in the hypercapnia-group during the intervention. Overall, median left ventricular ejection fraction was 45 % (IQR 38-55) without treatment group differences (p=0.2). Both invasive and echocardiographic assessment found increased cardiac index and stroke volumes in the hypercapnia-group (p <0.05). Right ventricular stroke work index (RVSWI) was consistently higher in the hypercapnia-group throughout the intervention (P-group < 0.001), while the pulmonary artery pulsatility index did not differ (P-group >0.05). Conclusions In patients resuscitated from OHCA, targeting mild hypercapnia compared to normocapnia was associated with increased TAPSE, S', FAC, TAPSE:PASP, RVSWI and cardiac index. Contrary to our prior concern these results indicate improved right ventricular function while targeting mild hypercapnia.