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.MethodsIn 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.ResultsThe 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).ConclusionsThe 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.