Background The mean age of patients with chronic hepatitis C virus (HCV) infection in the USA has been increasing. Despite the increasing proportion of HCV-infected elderly patients, this group is under-represented in clinical trials of HCV treatment. Aim We aimed to describe the real-world effectiveness of direct-acting antivirals (DAAs) among elderly patients. Patients and methods We retrospectively identified 17 487 HCV-infected patients who were started on treatment with sofosbuvir, ledipasvir/sofosbuvir, or paritaprevir/ombitasvir/ritonavir/dasabuvir-based regimens in the Veterans Affairs Healthcare System between 1 January 2014 and 30 June 2015. We ascertained sustained virologic response (SVR) rates in patients aged below 55, 55-59, 60-64, 65-69, 70-74, and 75 years or older and performed multivariable logistic regression to determine whether age predicted SVR. Results Overall unadjusted SVR rates were 91.2% [ 95% confidence interval (CI): 89.7-92.4], 89.8% (95% CI: 88.8-90.7), 90.8% (95% CI: 90.1-91.6), 91.1% (95% CI: 90.1-91.9), 90.0% (95% CI: 86.9-92.4), and 93.8% (95% CI: 88.8-96.7) in patients aged below 55, 55-59, 60-64, 65-69, 70-74, and 75 years or older. Unadjusted SVR rates were similar in all age groups after stratifying by genotype, treatment regimen, stage of liver disease, and treatment experience. In multivariate models, age was not predictive of SVR after adjusting for confounders. Conclusion DAAs produce high rates of SVR in all age groups, including patients in our oldest age category (>= 75 years). Advanced age in and of itself should not be considered a barrier to initiating DAA treatment. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.