OBJECTIVES: Conventional peginterferon-ribavirin antiviral treatment of chronic hepatitis C virus (HCV) often leads to anemia and neutropenia. Based on US claims data, we explored the incidence of both adverse events (AEs) and the associated risk factors, and assessed the related erythropoietin/granulocyte colony stimulating factor (G-CSF) costs in daily clinical practice. METHODS: Commercially insured patients with chronic HCV infection (ICD9 070.44,070.54,070.70,070.71) (all genotypes), who initiated any combination of (peg)interferon and/or ribavirin were identified in a large US claims database (Thomson 2006–2009). Time to first onset of anemia and neutropenia was analyzed using Kaplan-Meier and Cox proportional hazards regression. Anemia and neutropenia were defined based on ICD9-coding (280-285,288) and/or prescription of erythropoietin and G-CSF. RESULTS: 3,935 chronic HCV-infected patients (mean age 51.1, 63% male) initiated HCV treatment. 86% of the patients initiated a combination of peginterferon and ribavirin. Mean treatment duration was 245 days. Regardless of time on treatment, 32%/17% of the cohort experienced anemia/neutropenia respectively. Age, female gender, Charlson co-morbidity index and liver cirrhosis were predictive for both AEs. 20.3%/11.3% of the cohort received erythropoietin/G-CSF treatment respectively, on average for 131/126 days. The mean cost for the entire cohort to manage both AEs was $2,263 (erythropoietin) and $1,004 (G-CSF), which represents 12% of the overall healthcare cost in the follow-up year for the entire cohort. The majority of the costs associated with AE-related treatments (58%/54%) occurred after week 24 of therapy. CONCLUSIONS: Costs of managing anemia and neutropenia during HCV treatment are considerable and often continued beyond 24 weeks of treatment. New HCV treatment combinations allowing to shorten treatment up to 24 weeks, may considerably reduce AE-related costs. This reduction may be most important in treatment-naive genotype 1-infected patients, as the standard 48-week treatment duration is longer compared with other genotypes.