OBJECTIVES: To document disease-related resource utilization and costs by disease severity among persons with chronic hepatitis C virus (HCV) in a United States (US) managed care population. METHODS: A US insurance claims database spanning January 1, 2002 to December 31, 2006 was retrospectively analyzed. Patients with ≥1 diagnosis of chronic HCV and no evidence of hepatitis B were selected. Patients had continuous plan enrollment for ≥6 months before and ≥12 months following first observed HCV diagnosis. Disease severity, measured using the aspartate aminotransferase to platelet ratio index (APRI), was assessed for patients with valid lab results (N=2877). Patients were classified into three mutually exclusive severity categories: mild (APRI≤0.5, N=2384), moderate (0.51.5, N=116). Per patient use and costs of HCV-related medical services and prescriptions were assessed over 12 months post-diagnosis. RESULTS: More than 23% of patients with severe HCV had a disease-related hospitalization compared to 12% and 16% of mild and moderate patients, respectively (both P<0.05). Hospitalization costs were nearly 2.5 times higher in moderate patients ($3480) and approximately 4.7 times higher in severe patients ($6872) compared to those with mild disease ($1448; both P<0.01). Severe patients also had a significantly (P<0.01) higher mean number of hospital days (7.9) compared to moderate (6.7 days) and mild patients (4.1 days). There were no significant differences in encounters and costs for physician office and emergency department visits. Severe patients had slightly lower (but insignificant) HCV-related pharmacy costs compared to mild and moderate patients. After controlling for demographics and comorbidities in a multivariate analysis, mild patients incurred $4708 less (P<0.01) in total HCV-related costs compared to severe patients. CONCLUSIONS: Patients with moderate and severe HCV incur nearly twice the medical costs of patients with mild disease, due primarily to increased hospitalizations. There was no significant difference in ambulatory resource use and costs between moderate and severe patients.