Background/Purpose: Chronic heptitis C (CHC) shows a significant association with cirrhosis, and hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) is important in the diagnosis of HCC, but elevated AFP levels have also been observed in CHC without HCC. We evaluated the clinical correlation between elevated AFP levels and CHC. Methods: Prom April 1999 to November 2004, 654 CHC. patients with no evidence of HCC from imaging studies Were collected by chart review. Results: The prevalence of elevated AFP levels (>= 15 ng/mL) was 23.9%. Univariate analysis revealed that age histological activity index (HAI) fibrosis Score of 3/4, HAI inflammation score >= 7, aspartate amino-transferase (AST) and alanine transaminase (ALT) levels, AST/ALT ratio, and total bilirubin level were associated with elevated AFP levels. Multivariate analysis revealed that age (>= 55 vs. <55 years, HAI inflammation score (>= 7 vs. <7), ALT (> 150 U/L), and platelet count (<= 150 X 10(9) vs. >150 X 10(9) cells/L) were associated with elevated AFP levels. Multivariate analysis also revealed that hepatitis C virus (HCV) genotype 1b, platelet count <= 150 x 10(9) cells/L, AST > 80 U/L and AFP >= 6 ng/ml, were associated with advanced fibrosis. Using cut-off AFP level of > 6.0 ng.mL, the sensitivity and specificity of diagnosing fibrosis score 3/4 was 74.3% and 68.4%, respectively. Using a cut-off level of >= 15.0 ng/mL, the sensitivity mid specificity of diagnosing fibrosis score 3/4 was 35.7% and 91.1%, respectively. Conclusion: Elevated AFP levels were observed in 23.9% of patients with CHC, Elevated AFP levels correlated positively with age, HAI inflammation score, ALT elevation, and thrombocytopenia. In addition, HCV genotype 1b, thrombocytopenia AST elevation, and AFP level >= 6 ng/mL associated with advanced fibrosis. [J Formos Med Assoc 2009; 108(3); 210-218]