We used the United Network for Organ Sharing Database to determine the influence of antibody-based induction therapy on patient and graft survival in orthotopic liver transplant (OLT) recipients with and without hepatitis C (HCV). We identified all initial OLT patients with HCV serology. Patients were divided into four groups: HCV positive without induction (17 362), HCV positive with induction (3479), HCV negative without induction (20 417) and HCV negative with induction (4357). Both HCV positive and negative patients who received induction did better than those who did not. For HCV positive patients, 5-year patient survival was 70.8% versus 68.7% (p = 0.004) and graft survival was 65.2% versus 62.1% (p < 0.001). For HCV negative patients, 5-year patient survival was 78.8% versus 76.7% (p < 0.001) and graft survival was 74.0% versus 70.8% (p < 0.001). On multivariate analysis, induction was associated with improved patient (HR = 0.91: p = 0.024) and graft (HR = 0.88: p < 0.001) survival in HCV positive patients and improved patient (HR = 0.87: p = 0.003) and graft survival (HR = 0.87: p < 0.001) in HCV negative patients. The benefit of induction occurred early and largely dissipated when patients with death within a year were censored. The benefit of induction therapy appeared most pronounced in patients with renal insufficiency or on organ-perfusion support at transplant.