question: The role of upfront autologous stem cell transplantation (ASCT) remains unclear in patients with primary central nervous system lymphoma (PCNSL) receiving rituximab and high-dose methotrexate (MTX)-based chemotherapy. We analyzed the outcomes of upfront ASCT in 106 patients with PCNSL (median age, 64 years; range, 34-86) who received rituximab, MTX, vincristine, and prednisolone (R-MVP). The objective response rate was 88.7% (94/106) and included 46 complete responses (43.4%). Upfront ASCT was performed in 38 responders (median age, 51 years; range, 34-69), including 13 patients aged >60 years, after conditioning with busulfan (3.2 mg/kg, days 8 to 5) and thiotepa (5 mg/kg, days 4-3). For 56 responders ineligible for ASCT because of age >70 years, poor performance status, or refusal to undergo upfront ASCT, other consolidation treatments (n = 32) or observation (n = 24) were performed. With a median follow-up of 24.4 months (95% confidence interval, 20.7-28.0 months), no transplantation-related deaths occurred and seven patients relapsed after upfront ASCT. By contrast, 24 relapses occurred in patients who did not receive upfront ASCT. The progression-free and overall survival were significantly better in patients undergoing upfront ASCT (P = 0.001). Our real-world data suggest the benefit from upfront ASCT.