Abstract Background and Aim Direct‐acting antivirals (DAAs) have recently been developed to treat hepatitis C virus (HCV) infection. Additionally, interferon‐free DAA treatment has improved liver function and reduced the risk of hepatocellular carcinoma (HCC) following HCV eradication. Previous studies on HCV have focused mainly on the treatment rate and the risk of developing HCC, and less attention has been given to loss to follow‐up (LTFU) after DAA treatment. Therefore, the present study aimed to identify the definitive risk factors for LTFU after the start of DAA treatment. Methods Between September 2017 and March 2022, 296 patients receiving glecaprevir and pibrentasvir for HCV infection were enrolled in this study. The incidence of LTFU following DAA treatment and the risk factors contributing to LTFU were identified using the patients' clinical characteristics. Results In the present study, 75 patients (25.3%) interrupted their follow‐up visits. Multivariate logistic analysis revealed a history of injection drug use (hazard ratio [HR], 1.81; P = 0.017), treatment duration (8 weeks) (HR, 3.51; P = 0.0033), and age