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Summary: Treatment of Hepatitis C virus (HCV) in patients with severe renal insufficiency is cumbersome as sofosbuvir is mainly excreted by the kidneys. There is paucity of data on the use of sofosbuvir and NS5A inhibitors in these patients. We hereby report our experience of treating chronic hepatitis C in patients with severe renal insufficiency with full dose sofosbuvir and NS5A inhibitors. Forty‐seven patients with severe renal insufficiency (on dialysis n = 39, predialysis n = 8) with HCV infection were treated between December 2015‐August 2017 with full dose sofosbuvir with ledipasvir or daclatasvir for 12/24 weeks depending on the genotype and the presence or absence of cirrhosis. The distribution of HCV genotype was genotype 1 in 32 (68.1%), genotype 3 in 13 (27.7%) and 4 in 2 (4.3%) patients. Among 12 (25.5%) patients with cirrhosis, 7 (14.9%) were decompensated with ascites. All patients had end of treatment response, and sustained viral response at 12 weeks was achieved in 45 (95.7%) patients. There was significant improvement in liver stiffness at 3 months after treatment (8.8 (3.8‐42) to 7.1 (3.3‐24.1) kPa; (P = 0.047)). There was no change in haemoglobin and eGFR with treatment in predialysis group (haemoglobin‐ 10.2 ± 1.5 g/dL vs 9.6 ± 1.3 g/dL, P = 0.44; eGFR‐ 19.8 ± 9.4 mL/min vs 17.9 ± 8.5 mL/min, P = 0.67). Therapy was very well accepted. Full dose sofosbuvir with NS5A inhibitors is a well tolerated and effective therapy for HCV infection in severe renal insufficiency. [ABSTRACT FROM AUTHOR]