We investigated the accuracy of liver stiffness measurement (LSM) in chronic hepatitis C (CHC) in a multicenter, prospective study in South Korea. Between June 2005 and July 2009, 91 CHC patients without a previous history of antiviral treatment, clinical evidences of cirrhosis, coinfection with other viruses, and heavy alcohol consumption and with alanine aminotransferase (ALT) ≤5x upper limit of normal, total bilirubin ≤1.5 mg/dL, sufficient liver biopsy quality (≥15 mm and more than six portal tracts), interquartile range to median liver stiffness (LS) value ratio ≤0.21, and more than 10 valid measurements, were recruited. The Batts and Ludwig scoring system was used for histologic assessment. Age-platelet index (API), aspartate aminotransferase (AST)-to-platelet ratio index (APRI), and age-spleen-platelet ratio index (ASPRI) were calculated. Area under the receiver operating characteristic curve (AUROC) was used to evaluate the performance of LSM and other noninvasive models. The mean age was 47.9 years, and the mean LS value was 7.7 kPa (44 men and 47 women). LS value was highly correlated to the fibrosis stages (r=0.835, P<0.001). The AUROCs of LSM were 0.909 for ≥F2, 0.993 for ≥F3, and 0.970 for F=4 and were superior to those of API (0.72, 0.858, and 0.948, respectively), APRI (0.780, 0.887, and 0.904, respectively), and ASPRI (0.713, 0.862, and 0.957, respectively). The optimal cutoff LS values were 6.2 kPa for ≥F2, 7.7 kPa for ≥F3, and 11.0 kPa for F=4. Our data suggest that LSM can accurately assess liver fibrosis in patients with CHC and be applied in South Korea.