Objective: To evaluate predictive factors of treatment efficacy to interferon (IFN)/ribavirin in patients infected with HCV genotype 1b (HCV-1b). Methods: This study investigated pretreatment predictors, including viral- (aa substitutions in core aa 70/91 and NS5A-ISDR/IRRDR) and host-related factors (genetic variation near IL28B gene), to 48-week IFN/ribavirin in 490 Japanese adults infected with HCV-1b. Results: The proportion of patients who showed end-of-treatment response (ETR), sustained virological response (SVR), and SVR after ETR was 76, 54, and 76%, respectively. There was a significant positive correlation between the number of aa substitutions in ISDR and those in IRRDR. Concerning the substitution of core aa 91, the number of aa substitutions in ISDR/IRRDR of patients with Leu91 was significantly higher than that of patients with Met91. Furthermore, levels of viremia were influenced by aa substitutions in core aa 91 and ISDR/IRRDR. By multivariate analysis, rs8099917 genotype was an important predictor of ETR and SVR. With regard to viral factors, core aa 70/91 was an important predictor of ETR, and SVR after ETR. ISDR was an important predictor of SVR, and SVR after ETR. Conclusion: aa substitution in core/NS5A region and genetic variation near IL28B were important predictors of treatment efficacy to IFN/ribavirin.