The success of direct-acting antiviral (DAA) therapy has led to near-universal cure for patients chronically infected with hepatitis C virus (HCV) and improved post-liver transplant(LT) outcomes. We investigated the trends and outcomes of re-transplantation in HCV and non-HCV patients before and after the introduction of DAA. Adult patients who underwent re-LT were identified in the OPTN/UNOS database. Multi-organ transplants and patients with more than two total LTs were excluded. Two eras were defined, pre-DAA(2009-2012), and post-DAA(2014-2017). A total of 2,112 re-LT patients were eligible(HCV: n=499 pre-DAA and n=322 post-DAA; non-HCV: n=547 pre-DAA and n=744 post-DAA). HCV patients had both improved graft and patient survival after re-LT in the post-DAA era. One-year graft survival was 69.8% pre-DAA and 83.8% post-DAA(p<0.001). One-year patient survival was 73.1% pre-DAA and 86.2% post-DAA(p<0.001).Graft and patient survival was similar between eras for non-HCV patients. When adjusted, the post-DAA era represented an independent positive predictive factor for graft and patient survival(HR:0.67;p=0.005,and HR:0.65;p=0.004) only in HCV patients. The positive post-DAA era effect was observed only in HCV patients with first graft loss due to disease recurrence(HR:0.31;p=0.002, HR 0.32;p=0.003, respectively). Among HCV patients, receiving a re-LT in the post-DAA era was associated with improved patient and graft survival.This article is protected by copyright. All rights reserved.