Elevated serum low-density lipoprotein cholesterol (LDL-C) level has been associated with sustained virological response (SVR) by chronic hepatitis C patients treated with pegylated-interferon (PEG-IFN) α and ribavirin (RBV). The aim of this study was to investigate the relation between the baseline LDL-C level and the treatment outcome from telaprevir (TVR)-based triple therapy. This prospective, multicenter study consisted of 241 treatment-experienced patients infected with HCV genotype 1b. All received 12weeks of TVR in combination with 24weeks of PEG-IFNα2b and RBV. The SVR rate was 81.3% (196 of 241) by intention-to-treat analysis. Higher LDL-C level was strongly associated with SVR (P=1.3×10−8). The area under the receiver operating characteristic curve for predicting SVR was 0.78 and the cutoff value for the LDL-C level at baseline was 95mg/dL. In multivariable logistic regression analysis of predictors of SVR, LDL-C ⩾95mg/dL (odds ratio [OR] 3.60, P=0.0238), α-fetoprotein ⩽5.0ng/mL (OR 5.06, P=0.0060), prior relapse to PEG-IFNα and RBV (OR 5.71, P=0.0008), and rapid virological response (HCV RNA undetectable at week 4) (OR 5.52, P=0.0010) were extracted as independent predictors of SVR. For prior partial and null responders, the SVR rates of the groups with LDL-C ⩾95mg/dL were significantly higher than those of the <95mg/dL groups with IL28B TG/GG and pretreatment platelet count <150×109/L (both P<0.05). The baseline LDL-C level exerted a potent influence on the SVR of treatment-experienced patients treated with TVR-based triple therapy, especially for prior partial and null responders to PEG-IFNα and RBV.