The role of transplant nephrectomy after transplant failure is uncertain. We report the use and consequences of transplant nephrectomy among 19 107 transplant failure patients between 1995 and 2003 in the United States. Among 3707 patients with early transplant failure (graft survival <12 m), nephrectomy was performed in 56%, and was associated with an increased risk of death (HR 1.13, 95% CI 1.01-1.26). In contrast, among 15,400 patients with late transplant failure (graft survival > or =12 m), nephrectomy was performed in 27%, and was associated with a decreased risk of death (HR 0.89, 95% CI 0.83-0.95). In early transplant failure patients, nephrectomy was associated with a lower risk of repeat transplant failure (HR 0.72, 95% CI 0.56-0.94), while among late transplant failure patients; nephrectomy was associated with a higher risk of repeat transplant failure (HR 1.20, 95% CI 1.02-1.41). Definitive conclusions are not possible from this observational study. The role of nephrectomy in the management of dialysis treated transplant failure patients, and the implications of nephrectomy for repeat transplantation should be further studied in prospective studies.