Introduction: Direct antiviral agents (DAAs) are new drugs for the treatment of chronic hepatitis C virus (HCV) infection. These drugs are very effective and well tolerated. HCV can cause liver disease as well as extrahepatic manifestations, including a profound negative impact on health-related quality of life (HRQL). Aim of the study: To evaluate HRQL in the long term (> 6 months after finishing treatment) after successful treatment with DAAs. To the best of our knowledge, this is the first study that evaluates quality of life in the long term after DAA treatment. Material and methods: This is an observational study which included 100 patients treated with DAAs for chronic HCV infection between January 2015 and August 2018. Patients were assigned randomly. The average time after finishing treatment was 29.96 months. The Liver Disease Symptom Index (LDSI) 2.0 Questionnaire was used to evaluate quality of life before and after treatment. Results: Seven of 9 parameters of the LDSI 2.0 Questionnaire showed significant improvement in the long term after successful treatment with DAAs. Two parameters (arthralgia and jaundice) did not improve significantly. Quality of life improved in both males and females similarly. Improvement did not correlate with the severity of liver fibrosis. Conclusions: Treatment with DAAs improves HRQL significantly in the long term.