There is a paucity of large-scale data delineating outcomes and prognostication of older patients with primary central nervous system lymphoma (PCNSL). We retrospectively analyzed 539 newly-diagnosed PCNSL patients ages ≥60 years across 20 US academic centers. Median age was 70 years (range 60-88); at least one geriatric syndrome was present in 46%; median Cumulative Index Ratings Scale-Geriatrics (CIRS-G) score was 6 (range 0-27); and 36% had impairment in at least one activities of daily living (ADL). The most common induction regimens were high-dose methotrexate +/- rituximab; methotrexate, temozolomide, rituximab (MTR); and rituximab, methotrexate, procarbazine, vincristine (R-MPV). Overall, 70% of patients achieved remission with 14% undergoing consolidative autologous stem cell transplant (ASCT), and 24% receiving maintenance. With 58-month median follow-up, median progression-free survival (PFS) and overall survival (OS) were 17 months (95% CI 13-22 months) and 43 months (95% CI 31-56 months), respectively. Three-year PFS and OS were highest with MTR (55% and 74%, respectively). Wiith single-agent methotrexate +/- rituximab, 3-year PFS and OS were 30% (p=.0002) and 47% (p=.0072), respectively. On multivariate analysis, increasing age at diagnosis and ECOG performance status (PS) were associated with inferior PFS, and age, hypoalbuminemia, higher CIRS-G score, and ECOG PS adversely affected OS. Among patients receiving maintenance, 3-year PFS was 65% versus 45% without maintenance (P=0.02), with 3-year OS of 84% vs. 61%, respectively (P=.0003). Altogether, outcomes in older PCNSL patients appeared optimized with high-dose methotrexate combination induction as well as maintenance. Furthermore, several prognostic factors, including geriatric measures, were associated with divergent outcomes. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.