Hepatitis C virus infection is common among patients on hemodialysis therapy and is an important cause of morbidity and mortality. We investigated the safety and effectiveness of a paritaprevir/ritonavir/ombitasvir/dasabuvir regimen in a group of 10 patients on hemodialysis therapy with genotype 1a, 1b, or 4 hepatitis C virus infection who had predictors of unfavorable response, such as compensated cirrhosis (7 patients) or advanced fibrosis and failure of previous therapy (3 patients). The treatment, with or without ribavirin, was administered daily for 12 or 24 weeks. Clinical and virologic assessment was performed every 4 weeks during the treatment and at posttreatment weeks 4 and 12. All patients achieved a sustained virologic response at posttreatment week 12. 80% of patients reported at least one adverse event: fatigue and anemia of mild intensity were the most common; a single episode of moderate liver decompensation was observed. The paritaprevir/ritonavir/ombitasvir/dasabuvir antiviral regimen is effective and well tolerated in genotype 1 or 4 hepatitis C virus-infected patients on hemodialysis therapy with compensated cirrhosis and/or failure of previous treatments.