ObjectiveTo assess the safety and efficacy of direct antiviral drugs (DAAs) inhepatitis C virus (HCV) negative recipients undergoing kidney transplantation from HCV IgG (+) / HCVinfected renal allografts. MethodsA total number of 12 patients were enrolled in the Institute of OrganTransplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from 2018to 2023, including 10 patients who were preemptively started DAAs regimen immediately after transplantation, and 2 patients who were therapeutically given DAAs regimen after abnormal liver function anddetectable viral load. All patients had 12-week oral antiviral regimen of sofosbuvir/velpatasvir (SOF/VEL). Blood transaminase, serum creatinine, eGFR,drug concentration and HCV viral load were regularly reviewed to evaluate the efficacy and safety of DAAs. ResultsOne case of treatment failure occurred after the completion ofSOF/VEL therapy in 10 preemptively-treated patients, and the genotype was detected as 3b. The other 9 recipients achieved sustained virological response (SVR)12 weeks after the end of SOF/VEL treatment. After altering the antiviral regimen twice in succession, the patients who failed in the initial treatment ultimately achieved SVR12 with a DAAs combination containing ribavirin (RIB). Abnormal liver function and high HCV viral load were detected in 2 therapeutically treated patients one month after transplantation, the patients had normalized transaminase once SOF/VEL combination was started and achieved SVR12 eventually. The patients who failed to achieve SVR12 showed persistent abnormal bilirubin during the treatment of DAAs containing ribavirin. The serum creatinine and drug concentration of all patients were stable during the follow-up period. ConclusionIt is safe and effective for HCV uninfected recipients to receive HCV-positive kidney grafts with DAAs prophylactic or therapeutic therapy. For patients infected with subtype 3b HCV and failed in the initial treatment of pan-genotypic DAAs regime, a combination of SOF/VEL/RIB is recommended.