Multiple noninvasive methods have been used successfully in the prediction of fibrosis. However, their role in the prediction of response to hepatitis C virus (HCV) antiviral therapy is debatable. The aim of this study was to validate and compare the diagnostic performance of FibroScan, APRI (aspartate aminotransferase (AST)-to-platelet ratio index), FIB4, and GUCI (Göteborg University Cirrhosis Index) for the prediction of hepatic fibrosis and treatment outcome in HCV-infected patients receiving pegylated interferon and ribavirin (PEG-IFN/ribavirin).This study included 182 Egyptian patients with chronic HCV infection. They were classified into two groups based on the stages of fibrosis: mild to significant fibrosis (F1-F2) and advanced fibrosis (F3-F4). The APRI, FIB4, and GUCI scores were calculated before the antiviral treatment. The FibroScan was performed for all patients before treatment.Stiffness and FIB4 have greater sensitivity and specificity in detecting advanced fibrosis of 80%, 77% and 88%, 84%, respectively. Based on multivariate regression analysis, FIB4, body mass index (BMI), and alpha-fetoprotein (AFP) level were found to be statistically significant predictors of advanced fibrosis (p-value: 0.000, 0.011, and 0.001, respectively) with odds ratio (OR: 3.184, 1.170, and 1.241, respectively). With respect to virological response, the stiffness, APRI, FIB4, and GUCI were significantly lower in sustained virological responders. However, these are not good predictors of response to PEG-IFN/ribavirin therapy. AFP was the only statistically significant predictor of response (p=0.002) with OR of 1.141 in multivariate regression analysis.FibroScan and noninvasive scores such as APRI, FIB4, and GUCI can be used as good predictors of liver fibrosis in chronic hepatitis C. However, they are not good predictors of response to PEG-IFN/ribavirin therapy.