Objective To investigate whether mixed venous-arterial carbon dioxide difference (Pv-aCO2) combined with passive leg raising (PLR) could better guide volume management for patients post off-pump coronary artery bypass grafting (OPCABG).Methods Eighty patients experienced OPCABG, and admitted to Tianjin Chest Hospital from June 1st to October 1st in 2016 were enrolled. They were randomly divided into two groups: observation group given Pv-aCO2 combined with PLR directed therapy and control group given central venous pressure (CVP) directed therapy, 40 cases in each group. The difference in body temperature (T), heart rate (HR), mean arterial pressure (MAP), CVP, oxygenation index (PaO2/FiO2), mixed venous oxygen saturation (SvO2), Pv-aCO2, blood lactate (Lac), fluid intake, scores of the vasoactive agents at 6 hours post-operation, sequential organ failure assessment (SOFA) of 24 hours, mechanical ventilation time, the length of intensive care unit (ICU) stay, and hospitalization time were compared. The correlation between Pv-aCO2 and cardiac index (CI), Pv-aCO2 and Lac were analyzed by Spearman analysis in observation group.Results The T, HR, MAP, CVP, PaO2/FiO2, SvO2 and Lac at 6 hours post-operation were higher than those at admission in two groups, and Pv-aCO2 were significantly decreased. The SvO2 and fluid intake in observation group were higher than those in control group [SvO2: 0.671±0.068 vs. 0.634±0.052, fluid intake (mL): 454±151 vs. 304±106, bothP < 0.05], Pv-aCO2, Lac and scores of the vasoactive agents were lower than those in control group [Pv-aCO2 (mmHg, 1 mmHg = 0.133 kPa): 6.1±1.8 vs. 7.0±1.8, Lac (mmol/L): 1.7±0.5 vs. 2.8±0.6, scores of the vasoactive agents: 3.18±1.01 vs. 4.48±1.50, allP < 0.05], mechanical ventilation time and the length of ICU stay were less than those in the control group (hours: 16.52±6.41 vs. 21.96±9.00, 45.51±9.36 vs. 51.76±13.66, bothP< 0.05). There was no significant difference in SOFA, hospitalization time between the two groups. There was negative correlation with Pv-aCO2 and CI (r = -0.752,P < 0.01), and no correlation with Pv-aCO2 and Lac (r = -0.154,P = 0.171).Conclusion Pv-aCO2 combined with PLR can better guide volume management in the patients post OPCABG, reduce the usage of vasoactive agents and decrease the mechanical ventilation time and the length of ICU stay.