Objective: Protein-losing enteropathy (PLE) is devastating sequela of Fontan operation, of which pathophysiology is poorly understood and treatment is incomplete. Hepatocyte growth factor (HGF) is known as potent lymphangiogenetic factor. The purpose of this study was to evaluate the potential role of HGF in the development of PLE after Fontan operation. Methods: Twenty-nine patients who underwent Fontan operation were enrolled in this study. Among them, 10 patients were under the treatment of PLE and 19 patients showed no evidence of PLE. We reviewed medical records and measured serum HGF, vascular endothelial growth factor (VEGF), heparin, albumin, random stool 慣-1 antitrypsin concentration and other factors. We also checked echocardiogram to evaluate hemodynamic status including ventricular function and cardiac index. Results: Mean age was 15.7짹8.7 in the patients and 17.0짹6.6 year-old in the controls. Serum albumin level was significantly lower in the patients than the controls (2.82짹0.96 versus 4.28짹0.36 g/dL, p<0.001) and stool 慣-1 antitrypsin concentration was significantly higher in the patients than the controls (116.4짹108.3 versus 5.1짹3.2 mg/dL, p<0.001). Serum HGF was significantly higher in the patients than the controls (0.61짹0.27 versus 0.42짹0.12 ng/mL, p=0.031). There was no significant difference of serum VEGF and heparin between two groups. Elevated serum HGF showed significant correlation with decreased serum albumin (r=-0.474, p=0.011) and borderline significance in the correlation with increased stool 慣-1 antitrypsin concentration (r=0.365, p=0.067). Conclusions: Increased circulating HGF may play a role in the development of PLE after Fontan operation. Further studies about the role of HGF in the PLE pathogenesis are needed.