HCV-infected patients with cirrhosis achieve high sustained virological response (SVR) rates with direct-acting antivirals (DAAs) even after hepatic decompensation. We aimed to assess the clinical outcome following DAAs among patients with compensated and decompensated cirrhosis in relation to SVR and changes in MELD score.d chronic HCV-infected patients with cirrhosis from 4 hepatology clinics were included. The primary endpoint in survival analyses was clinical disease progression, defined as liver failure, hepatocellular carcinoma, liver transplantation or death.In total, 868 patients were included with a median age of 59 (IRQ 54-65) years; 719 (83%) with CP-A cirrhosis and 149 (17%) with CP-B/C cirrhosis. SVR was attained by 647 (90%) CP-A patients and 120 (81%) CP-B/C patients. During a median follow-up of 28 (IQR 20-36) months, 102 (14%) CP-A patients and 96 (64%) CP-B/C patients experienced clinical disease progression. SVR was independently associated with an improved event-free survival in patients with CP-A cirrhosis (adjusted HR 0.47, 95%CI 0.27-0.82, p=0.007), but not in patients with CP-B/C cirrhosis (adjusted HR 1.23, 95% CI 0.67-2.26, p=0.51). Twelve weeks post-DAAs, 28 (19%) patients with CP-B/C cirrhosis had ≥2-point MELD decline, but their 2-year event-free survival did not differ from those with a stable MELD (47.9% [95%CI 28.7-67.1] vs 48.9% [95%CI 38.1-59.7], respectively, p=0.99).Among patients with chronic HCV infection, DAA-induced SVR was associated with a reduced risk of clinical disease progression in patients with CP-A cirrhosis but not in patients with CP-B/C cirrhosis. In CP-B/C cirrhosis, a ≥2-point MELD decline did not translate to improved clinical outcome.