We report the case of a 45-year-old man with HCV treated with pegylated interferon-alpha/ribavirin, in whom fatal cardiomyopathy occurred. Cardiomyopathy is a rare complication of high dose of standard interferon but has never been reported with pegylated interferon. The relationship between pegylated interferon-alpha/ribavirin and the development of cardiomyopathy is highly probable for the following reasons: (1) a cardiologist consultation with specific investigations had been performed before treatment excluding a pre-existing cardiomyopathy; (2) symptoms of advanced dilated cardiomyopathy appeared immediately after the end of treatment; (3) other causes of cardiomyopathy have been ruled out. In all except one of the 21 reported cases with standard interferon, cardiomyopathy was reversible. In our patient, fatal cardiomyopathy occurred with a usual dose of pegylated interferon-alpha. Clinicians should be aware of this potential complication when evaluating the ratio benefit/risk of treatment in patients with chronic hepatitis C infection.