Under-recognition and under-treatment of chronic hepatitis C virus (HCV) infection is an important determinant of the disease outcome. The aim of this study was to investigate the treatment rate and factor of initiation of interferon-based antiviral treatment for chronic hepatitis C patients in a prospective, multicenter Korean HCV cohort. Treatment-naïve 759 patients with chronic HCV infection were prospectively followed from January 2007–2013 at six university hospitals during a median (interquartile range) follow-up of 769 (76–1,427) days. The subjects consisted of patients with chronic hepatitis C (n = 553, 72.9%), liver cirrhosis (n = 127, 16.7%), and hepatocellular carcinoma (n = 79, 10.4%), and were treated usually using pegylated interferon alpha and ribavirin. Treatment initiation rate and its related factors were analysed. The initiation rate of antiviral treatment was 37.3% (n = 273), and the cumulative probability of treatment initiation over 5 years was 39.4%. Multivariate analysis showed that age <58 years (hazard ratio [HR] = 1.588, 95% CI = 1.151–2.193), job employment (HR = 1.737, 95% CI = 1.279–2.363), absence of HCC (chronic hepatitis, HR = 2.534, 95% CI = 1.003–6.400; liver cirrhosis, HR = 2.873, 95% CI = 1.101–7.494), alanine transaminase (ALT) >40 IU/L (HR = 1.682, 95% CI = 1.228–2.303), and genotype 2 (HR = 1.364, 95% CI = 1.034–1.798) were independent factors related to treatment initiation. Interferon-based antiviral treatment was initiated in more than one third of chronic HCV infected patients visiting university hospitals, who were young, employed, HCV genotype 2, and with abnormal ALT without HCC, in Korea. J. Med. Virol. 88:275–281, 2016. © 2015 Wiley Periodicals, Inc.