BACKGROUND: High plasma levels of interferon-gamma inducible protein-10 (IP-10) have been shown to be associated with impaired treatment response in chronic hepatitis C virus (HCV) infection. Whether IP-10 levels predict treatment in acute HCV infection is unknown. METHODS: Patients with acute or early chronic HCV infection from the Australian Trial in Acute Hepatitis C (ATAHC) cohort were evaluated. Baseline and on-treatment plasma IP-10 levels were measured by ELISA. IL28B genotype was determined by sequencing. RESULTS: Overall, 74 HCV mono-infected and 35 HIV/HCV co-infected patients were treated in ATAHC, of whom 89 were adherent to therapy and were included for analysis. IP-10 levels correlated with HCV RNA levels at baseline (r = 0.48, P<0.001) and during treatment. Baseline IP-10 levels were higher in patients who failed to achieve rapid virological response (RVR). Only one patient with a plasma IP-10 level >600 pg/mL achieved RVR. There was no association with IP-10 levels and early virological response (EVR) or sustained virological response (SVR). CONCLUSIONS: Baseline IP-10 levels are associated with early viral kinetics but not ultimate treatment outcome in acute HCV infection. Given previous data showing that patients with high baseline IP-10 are unlikely to spontaneously clear acute HCV infection, they should be prioritized for early antiviral therapy.