Background. PCNSL is mainly treated with HD-MTX-based chemotherapy with or without WBRT. However, As WBRT is associated with delayed neurotoxicity leading to dementia in the elderly, many institutes reported benefits of intensive chemotherapy or high-dose chemotherapy with ASCT. We investigated whether treatment with HD-MTX and rituximab, followed by continued-maintenance HD-MTX monotherapy (3.5g / m2), improves overall survival (OS). Methods. In this retrospective, single-center trial 52 immunocompetent patients with newly diagnosed PCNSL were included. All were treated between January 2005 and December 2017. The controls were 18 patients who, between 2005 and 2011, had received 3 cycles of HD-MTX and then adjuvant treatment with WBRT. In 2011 we started HD-MTX continued-maintenance therapy to treat 34 PCNSL patients. In the induction phase, these patients received HD-MTX every 14 days until a complete response (CR) was observed. When CR was obtained, maintenance therapy with HD-MTX (3.5g / m2) was delivered every three months. Results. In 3-year overall survival (OS) there was a statistically significant difference between the two groups [controls : 33.1% (95%, CI 12.4 - 55.7%) ; maintenance group : 74.9% (95%, CI 55.6 - 86.7%) (p < 0.02)]. Conclusion : The induction of HD-MTX based chemotherapy followed by continued-maintenance HD-MTX monotherapy improved OS compared with chemoradiotherapy consisting of HD-MTX followed by WBRT. J. Med. Invest. 68 : 286-291, August, 2021