We tested our hypotheses that central venous pressure (CVP) shows an excessive increase in response to volume overload in Fontan circulation according to the extent of the reduction in venous capacitance (Cv), and that the maximum CVP after volume loading is associated with hepatic congestion. Changes in CVP after angiography (volume loading) were examined in 40 patients with Fontan circulation and 29 controls with biventricular circulation. CVP significantly increased with angiography in both groups, but the changes were much more evident in the Fontan group than in controls (3.3 ± 2.0 vs. 0.9 ± 1.4 mmHg, p = 0.0003). Multivariate analysis demonstrated that reduced Cv was the only significant determinant of CVP increase, independent of the amount of injected contrast medium, blood volume, pulmonary resistance, and ventricular diastolic stiffness (p < 0.05). Importantly, the use of a venodilator was associated with increased Cv and the resultant suppression of CVP elevation with volume load. In addition, CVP levels both at baseline (p = 0.02) and after volume loading (p = 0.01) were weakly but significantly correlated with the plasma levels of γ-glutamyl transpeptidase, a marker of hepatic congestion; however, multivariate analysis revealed that the CVP level after volume loading was a more important determinant of hepatic congestion. The results of this study highlight the importance of assessing dynamic in addition to static CVP for a better understanding of Fontan circulation. The potential importance of Cv as a therapeutic target for improving Fontan physiology needs further elucidation.