Introduction: Data of minimal hepatic encephalopathy (MHE) before and after hepatitis C virus (HCV) treatment remain scarce. We aimed to describe the prevalence, evolution and predictive factors of MHE before and after a sustained virological response (SVR). Material and methods: It was a prospective study that included adults with cirrhosis due to HCV treated by direct-acting agents (DAA). MHE was assessed using the Psychometric Hepatic Encephalopathy Score (PHES). Results: 104 patients (65% female, age 60 ±10 years; 69% with diabetes, 47% with hypertension; 82% ChildPugh A) were included. MHE was assessed just before therapy and 12 (IQR 7-15) months after SVR. Prevalence of MHE before HCV treatment and after SVR were 16% and 22%, respectively (p = 0.18). Resolution of MHE after SVR occurred in afew patients (n = 4/17) and 10 of 87 patients (11.5%) without MHE before treatment developed this condition after SVR. MHE after SVR was more common in patients with MHE before treatment (57% vs. 5%, p < 0.001). In multivariate analysis, older age, hypertension and hypoalbuminemia after treatment were predictors of MHE after SVR. In the absence of all these variables, none of the patients had MHE. In contrast, the prevalence of MHE was 42% and 70% in the case of presence of any 2 of these factors and all these conditions, respectively. Conclusions: MHE is frequent in patients with cirrhosis who achieved SVR after DAA. SVR is associated with low probability of resolution of MHE and may not entirely protect patients from developing de novo MHE. Presence of MHE before DAA, older age, hypertension and hypoalbuminemia after SVR were independently associated with this condition.