SummaryWe followed for 2 years patients treated with direct‐acting agents (DAA) to assess long‐term durability of virologic response, improvement of liver function, reduction in liver stiffness (LS) and risk of hepatocellular carcinoma (HCC). The study included patients from 16 hepatologic centres involved in the AMBER, investigator‐initiated study on treatment of chronic hepatitis C patients within a programme preceding EU registration of ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin. A total of 204 patients among 209 from the primary study were enrolled, 200 with available testing at 2‐year follow‐up (2yFU) with undetectable HCV RNA (198 responders and 2 nonresponders retreated). During 2yFU, 4 patients died, 17 had hepatic decompensation and 3 needed liver transplantation. De novo hepatocellular carcinoma was diagnosed in 4 and its recurrence in 3 patients. Significant decreases in bilirubin, MELD, Child‐Pugh scores and liver stiffness, and increases in albumin level were observed during 2yFU. Strengths of the study were a fixed period of post‐treatment follow‐up, prospective character of the study and high proportion of available patients from the primary study. The major weaknesses were lack of a comparative arm and relatively insufficient number of patients for subsets analysis. In conclusion, 2‐year follow‐up confirmed durability of virologic response after treatment of HCV infection with ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin. It was accompanied by significant improvement of major measures of hepatic function and reduction of hepatic stiffness. Successful therapy did not prevent hepatic decompensation, HCC or death in cirrhotics that support the need for longer than 2‐year monitoring for possible disease progression.