© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons Direct-acting antivirals approved for use in patients with end-stage renal disease (ESRD) now exist. HCV-positive (HCV+) ESRD patients have the opportunity to decrease the waiting times for transplantation by accepting HCV-infected kidneys. The optimal timing for HCV treatment (pre- vs posttransplant) among kidney transplant candidates is unknown. Monte Carlo microsimulation of 100 000 candidates was used to examine the cost-effectiveness of HCV treatment pretransplant vs posttransplant by liver fibrosis stage and waiting time over a lifetime time horizon using 2 regimens approved for ESRD patients. Treatment pretransplant yielded higher quality-adjusted life years (QALYs) compared with posttransplant treatment in all subgroups except those with Meta-analysis of Histological Data in Viral Hepatitis stage F0 (pretransplant: 5.7 QALYs vs posttransplant: 5.8 QALYs). However, treatment posttransplant was cost-saving due to decreased dialysis duration with the use of HCV-infected kidneys (pretransplant: $735 700 vs posttransplant: $682 400). Using a willingness-to-pay threshold of $100 000, treatment pretransplant was not cost-effective except for those with Meta-analysis of Histological Data in Viral Hepatitis stage F3 whose fibrosis progression was halted. If HCV+ candidates had access to HCV-infected donors and were transplanted ≥9 months sooner than HCV-negative candidates, treatment pretransplant was no longer cost-effective (incremental cost-effectiveness ratio [ICER]: $107 100). In conclusion, optimal timing of treatment depends on fibrosis stage and access to HCV+ kidneys but generally favors posttransplant HCV eradication.