Background & Aims: Sofosbuvir (SOF) and weight-based ribarivin (RBV) represented until recently the standard of care in hepatitis C virus (HCV) genotype (GT)2 patients. In registration studies 12-16 weeks duration were associated with a 90% sustained virological response at 12 weeks (SVR12). Real life cohorts showed lower SVR12 rates. Methods: SVR12 rates attained in an Italian real life cohort and possible benefits of a duration extended up to 20 weeks was investigated in HCV GT2 patients with cirrhosis. The role of 2k/1b chimeras as potential predictor of treatment failure was also analysed. Results: Overall, 291 HCV GT2 infected patients with bridging fibrosis or cirrhosis were evaluated. Median age was 68 years (18-87); 163 were treatment naive. Of 168 cirrhotic patients, 149 had Child-Pugh score A and 19 B, 50 platelets count <100,000/mm(3) and 62 albumin <3.5 g/dl. SVR12 were 95.53% overall, with 99.15% in non-cirrhotic patients and 93.06% in cirrhotic patients. In patients who completed treatment, SVR rates for cirrhotic patients resulted in 94.51%, and 94.94% after 16 or 20 weeks respectively. Predictors of SVR were low platelet count and esophageal varices (OR 7.2; 95% CI 1.67-31.25; p = 0.0022 and OR 0.1; 95% CI 0.01-0.72; p = 0.0079, respectively). Anemia was mild in 12.4%, moderate in 3.4%, and severe in 2.4% of cases. Anemia was slightly more frequent among longer duration but not associated with treatment discontinuations. No 2k/1b strains or genotypes different from those at baseline were identified at relapse. Conclusions: In GT2 cirrhotic patients, SOF/RBV for 16 or 20 weeks is associated with real life SVR12 rates of 95%. Lay summary: A duration of treatment of 16-20 weeks was recommended for treatment of HCV GT2 patients using the combination of sofosbuvir and ribavirin. Real life experiences, where patients received 12 weeks of treatment regardless of the severity of liver disease, suggested that response rates are lower than expected, in particular in patients with liver cirrhosis. A misleading genotyping of a 2k/1b strain as GT2 was also hypothesized as a further explanation for less effectiveness. We demonstrated that using the recommended extended duration in patients with more severe disease 95% of patients with severe liver disease including cirrhosis can be cured and that 2k/1b strain plays only a secondary role in specific countries like Germany. Although this combination has been recently replaced by sofosbuvir and velpatasvir fixed dose combination as the standard of care for treating HCV GT2 patients, our findings may inform physicians from countries where the new regimen is not yet available. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved.