AIM:Biliary atresia (BA) is a neonatal liver disease defined as chronic progressive fibrotic obliteration of extrahepatic bile ducts. The objective of this study was to determine the association of serum connective tissue growth factor (CTGF) with clinical outcome and liver stiffness measurement. METHODS:Eighty-two BA patients post-Kasai operation and 28 healthy controls were recruited. BA patients were categorized into two groups based on their portal hypertension (PH) status. Serum CTGF levels were determined by enzyme-linked immunosorbent assay. Liver stiffness scores were measured by transient elastography. RESULTS:BA patients had greater CTGF levels (905.9 ± 57.7 vs 238.3 ± 23.5 pg/mL, P < 0.001) and higher liver stiffness values than controls (28.2 ± 2.6 vs 5.0 ± 0.5 kPa, P < 0.001). Serum CTGF levels were remarkably elevated in BA patients with PH compared to those without PH (1092.4 ± 73.9 vs 582.6 ± 45.7 pg/mL, P < 0.001). Furthermore, BA patients with PH had significantly higher liver stiffness values compared to those without PH (37.3 ± 3.0 vs 10.6 ± 1.1 kPa, P < 0.001). Additionally, serum CTGF was positively correlated with liver stiffness (r = 0.875, P < 0.001) and total bilirubin (r = 0.462, P < 0.001). There was an inverse correlation between serum CTGF and serum albumin (r = -0.579, P < 0.001). CONCLUSION:High serum CTGF was associated with a poor outcome in BA patients. Accordingly, serum CTGF and transient elastography may serve as non-invasive biomarkers reflecting the disease severity in postoperative BA patients.