Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation. Hepatitis C virus (HCV) infection has been linked to increased risk of lymphoma among immunocompetent individuals. We therefore investigated the association between HCV infection and PTLD in a retrospective cohort study of all individuals in the United States who received their first solid organ transplant from 1994 to 2005 (N = 210 763) using Scientific Registry of Transplant Recipients data. During follow-up, 1630 patients with PTLD were diagnosed. HCV prevalence at transplantation was 11.3%. HCV infection did not increase PTLD risk in the total cohort (Cox regression model, hazard ratio [HR] = 0.84; 95% confidence interval [CI] 0.68-1.05), even after adjustment for type of organ transplanted, indication for transplantation, degree of HLA mismatch, donor type, or use of immunosuppression medications. Additional analyses also revealed no association by PTLD subtype (defined by site, pathology, cell type, and tumor Epstein-Barr virus [EBV] status). HCV infection did increase PTLD risk among the 2.8% of patients (N = 5959) who were not reported to have received immunosuppression maintenance medications prior to hospital discharge (HR = 3.09; 95% CI, 1.14-8.42; P interaction = .007). Our findings suggest that HCV is not a major risk factor for PTLD, which is consistent with the model in which an intact immune system is necessary for development of HCV-related lymphoproliferation.