Background: Depression and anxiety have been associated with interferon treatment and low treatment adherence. Aim: To study the incidence and associated risk factors of depressive and anxiety disorders during pegylated interferon plus ribavirin and treatment adherence in a prospective cohort of 176 patients with chronic hepatitis C patients. Methods: Patients were interviewed at baseline using the Structured Clinical Interview for DSM-IV Mental Disorders and the Patient Health Questionnaire and the Hospital Anxiety and Depression Scale were completed. Both questionnaires were completed also after 4, 12 and 24 weeks of treatment. Results: De novo depressive and/or anxiety disorders were diagnosed in 53 (36%) patients, in whom antidepressants and/or anxiolytics were administered. Higher baseline depression-subscale score (OR = 27.8, 95% CI = 2.82-333), primary education level (OR = 3.1, 95% CI = 1.40-7.03) and being an immigrant (OR = 3.2, 95% CI = 1.12-9.47) were predictors of psychiatric disorders during anti-viral therapy. The percentage of patients with good adherence was lower in those with depression and/or anxiety (79% vs. 90%, P < 0.04). Only one patient (1%) discontinued treatment because of a major depressive episode. Depression and/or anxiety disorders had no effect on attainment of sustained virological response. Conclusion: Early detection and treatment of depressive and anxiety disorders favours good adherence to anti-viral treatment in hepatitis C. © 2008 The Authors.