Background: Fontan circulation may be, in part, characterized by portal hypertension that can be estimated by hepatic vein wedge pressure (HWP). Purpose: To evaluate associations of HWP in cosecutive 318 Fontan patients (18±7 years old) during catheterization and compared the results with the hemodynamics, liver function and the related plasma biomarkers. HWP significantly correlated positively with inferior vena cava pressure (IVCP), pulmonary artery resistance (Rp), ration of Rp to systemic artery resistance (Rs) (Rp/Rs), and cardiac index and negatively with Rs and arterial and mixed venous oxgen saturations. Of those, high IVCP, low Rp and high Rp/Rs were independently correlated with high HWP (p Conclusion: High HWP associates with a significant reduction of Rp and Rs with preserved cardiac output. This unique Fontan circulation with Rs-dominant reduction may be due to both portal hypertension and overproduction of nitric oxide secondary to liver dysfunction.