Background/AimsThe association between depression and chronic hepatitis C virus (HCV) infection or pegylated interferon α and ribavirin therapy (PR therapy) has not been extensively studied in Korea. We aimed to clarify the prevalence of depression and its incidence during PR therapy in chronic hepatitis C (CHC) patients.Methods : In this prospective, multicenter study, 114 CHC patients were screened for depression using two self-reported scales, the Beck Depression Inventory-I (BDI-I) and the Hospital Anxiety and Depression scale (HADS). The incidence of depression during PR therapy was evaluated in 62 patients who underwent PR therapy during the study period.Results : The prevalence of baseline depression was 17.5% according to the BDI-I score ≥10 criterion and 4.4% according to the HADS-D score ≥8 criterion in the 114 CHC patients, and it was significantly associated with an unmarried state. During PR therapy, depression developed in 34.6% according to the BDI-I scale and 29.5% according to the HADS-D, which negatively affected sustained virologic response (SVR).Conclusion : sThe prevalence of depression in Korean CHC patients appears to be low compared to that in Western patients; however, its incidence during PR therapy (approximately 30%) was similar to that of other populations, which led to a lower SVR rate. Active screening and multidisciplinary management of depression during PR therapy is warranted.