The elderly people, 65 years old and above, are growing in number. The structural and functional changes associated with aging place the elderly at risk when challenged by extracorporeal therapies, such as therapeutic plasma exchange (TPE). We retrospectively analyzed data on all patients who underwent TPE for renal indications at our institution between January 1, 2000 and June 30, 2010 and compared renal indications and mortality associated with the use of TPE in older versus younger patients. During this period, 621 patients underwent 4722 sessions of TPE. Of them, 191 patients were elderly (30.7%) and they underwent 1289 sessions (27.3%) of TPE. A total of 104 patients (16.7%) underwent 593 sessions of TPE because of renal-related indications: 26 patients in the elderly group and 78 in the younger. Side effects of dyspnea and hypotension were documented in only two patients, both in the elderly cohort. The main indication for TPE in the elderly was glomerulonephritis (GN) as compared with renal allograft rejection in the younger cohort, with a trend toward more death in the elderly (p = 0.07). The multivariable regression model which included age as a category, serum albumin, and initial serum creatinine were unable to predict mortality in this group of patients. In our experience, the main renal indications for TPE in elderly are different from those for younger patients, with GN being the most common renal indication in the elderly. The TPE used for renal indications in the elderly is relatively safe. Trends toward death in the elderly may be multifactorial and not necessarily related to TPE.