Polymorphisms of the inosine triphosphatase (ITPA) gene influence anemia during pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy, but their effects during triple therapy with PEG-IFN, RBV, and telaprevir are not known. Triple therapy for 12 weeks, followed by PEG-IFN and RBV for 12 weeks, was given to 49 patients with RBV-sensitive (CC at rs1127354) and 12 with RBV-resistant (CA/AA) ITPA genotypes who had been infected with hepatitis C virus (HCV) of genotype 1. Decreases in hemoglobin levels were greater in patients with CC than CA/AA genotypes at week 2 (21.63 6 0.92 vs. 20.48 6 0.75 g/dL, P 5 0.001) and week 4 (23.5 6 1.1 vs. 22.2 6 0.96, P 5 0.001), as well as at the end of treatment (22.9 6 1.1 vs. 22.0 6 0.86, P 5 0.013). Risk factors for hemoglobin <11.0 g/dL at week 4 were female gender, age >50 years, body mass index (BMI) <23, and CC at rs1127354 by multivariate analysis. RBV dose during the first 12 weeks was smaller in patients with CC than CA/AA genotypes (52 6 14% vs. 65 6 21% of the target dose, P 5 0.039), but the total RBV dose was no different between them (49 6 17% and 54 6 18% of the target, P 5 0.531). Sustained virological response (SVR) was achieved in 70% and 64% of them, respectively (P 5 0.724). Conclusion: ITPA polymorphism influences hemoglobin levels during triple therapy, particularly during the first 12 weeks while telaprevir is given. With careful monitoring of anemia and prompt adjustment of RBV dose, SVR can be achieved comparably frequently between patients with CC and CA/AA genotypes. (HEPATOLOGY 2011;53:415-421