Multiple myeloma (MM) typically afflicts elderly patients with a median age of 65 years. However, while recently shown to provide superior outcome to standard treatment, high-dose therapy (HDT) has usually been limited to patients up to 65 years. Among 550 patients with MM and a minimum follow-up of 18 months, 49 aged >/=65 years were identified (median age, 67; range, 65 to 76 years). Their outcome was compared with 49 younger pair mates (median, 52; range, 37 to 64 years) selected among the remaining 501 younger patients (<65 years) matched for five previously recognized critical prognostic factors (cytogenetics, beta2-microglobulin, C-reactive protein, albumin, creatinine). Nearly one half had been treated for more than 1 year with standard therapy and about one third had refractory MM. All patients received high-dose melphalan-based therapy; 76% of the younger and 65% of the older group completed a second transplant (P =.3). Sufficient peripheral blood stem cells to support two HDT cycles (CD34 > 5 x 10(6)/kg) were available in 83% of younger and 73% of older patients (P =.2). After HDT, hematopoietic recovery to critical levels of granulocytes (>500/microL) and of platelets (>50,000/microL) proceeded at comparable rates among younger and older subjects with both first and second HDT. The frequency of extramedullary toxicities was comparable. Treatment-related mortality with the first HDT cycle was 2% in younger and 8% among older subjects, whereas no mortality was encountered with the second transplant procedure. Comparing younger/older subjects, median durations of event-free and overall survival were 2.8/1.5 years (P =.2) and 4.8/3.3 years (P =.4). Multivariate analysis showed pretransplant cytogenetics and beta2-microglobulin levels as critical prognostic features for both event-free and overall survival, whereas age was insignificant for both endpoints (P =.2/.8). Thus, age is not a biologically adverse parameter for patients with MM receiving high-dose melphalan-based therapy with peripheral blood stem cell support and, hence, should not constitute an exclusion criterion for participation in what appears to be superior therapy for symptomatic MM.