Survival benefit (SB) for first liver transplantation (LT) is favorable at Model for End-Stage Liver Disease (MELD)≥15. Herein, we identify the MELD threshold for SB from repeat liver transplantation (ReLT) by recipient hepatitis C virus (HCV) status and donor risk index (DRI). We analyzed lab MELD scores in new United Network for Organ Sharing registrants for ReLT from March 2002 to January 2010. Risk of ReLT graft failure≤1 year versus waitlist mortality was calculated using Cox regression, adjusting for recipient characteristics. Of 3057 ReLT candidates, 54% had HCV and 606 died while listed. There were 1985 ReLT recipients, 52% had HCV and 567 ReLT graft failures by 1 year. Unadjusted waitlist mortality and post-ReLT graft failure rates were 416 (95% confidence interval [CI] 384-450) and 375 (95% CI 345-407) per 1000 patient-years, respectively. Waitlist mortality was higher with increasing waitlist MELD (p<0.001). The MELD for SB from ReLT overall was 21 (21 in non-HCV and 24 in HCV patients). MELD for SB varied by DRI in HCV patients (MELD 21, 24 and 27 for low, medium and high DRI, respectively) but did not vary for non-HCV patients. Compared to first LT, ReLT requires a higher MELD threshold to achieve an SB resulting in a narrower therapeutic window to optimize the utility of scarce liver grafts.