We examined the prevalence and nature of perceived problems in the interaction between physicians and patients diagnosed with hepatitis C virus (HCV) infection. This cross-sectional study included 322 outpatients diagnosed with chronic HCV infection and treated at a tertiary referral hospital's hepatology clinic. Patients were asked to provide demographic information and to complete a semistructured interview, the Sickness Impact Profile (SIP) and Hospital Anxiety Depression (HAD) scale. A team of two blinded coders analyzed the interviews. A total of 131 (41%) study patients reported communication difficulties with physicians involved in their care. The main difficulties were the poor communication skills of physicians (91 [28%]), physician incompetence regarding the diagnosis and treatment of HCV infection (74 [23%]), feelings of being misdiagnosed, misled, or abandoned (51 [16%]), or being stigmatized by their physician (29 [9%]). Patients were twice as likely to report difficulties with subspecialists as compared with generalists. Nonresponse with antiviral therapy correlated with perceived physician conflict even after adjusting for treatment in relation to the time of interview, whereas previous or ongoing substance abuse and mode of acquisition did not. In a multivariate model, patients' psychosocial problems were the best predictors of communication difficulties. In conclusion, a substantial number of patients with HCV infection report difficulties when interacting with physicians, which may be due to coexisting emotional or social problems. However, perceived stigmatization by physicians and a sense of abandonment reflect the need for further educational efforts. These should target both specialists and primary care providers to inform them about the psychosocial challenges facing these patients.