The transplantation of organs from donors with hepatitis C viraemia is typically avoided, but the advent of direct-acting antiviral (DAA) agents could prevent transmission of HCV to the recipient and enable the use of HCV-infected organs. In a US-based open label trial, 44 patients without HCV infection received organ transplantations (36 lungs, 8 hearts) from HCV-infected donors, immediately followed by a 4-week regimen of a pangenotypic DAA agent. Of the 35 patients with at least 6 months of follow-up, all had excellent graft function with a sustained undetectable hepatitis C viral load from ~2 weeks after transplantation. Thus, this approach of preventing establishment of HCV infection with DAA therapy could increase the available donor organ pool.