Introduction: The prognosis of patients (pts) with diffuse large B-cell lymphoma (DLBCL) and involvement of the central nervous system (CNS) remains dismal. Anti-CD19 chimeric antigen receptor T-cells (CART) are considered standard treatment for pts with refractory or relapsed (r/r) DLBCL. Pts with involvement of the CNS were excluded from most CART trials; however, anecdotal reports suggest that CART might be an effective treatment option for such pts. This EBMT registry study aimed at compiling data of a larger cohort of pts with primary (PCNSL) or secondary CNS lymphoma (SCNCL) to better define the role of CART in these settings. Methods: All centres contributing to the EBMT database were asked for consecutive cases of PCNSL and SCNSL, which had been treated with any type of CART between January 2018 and December 2021. Reported pts were identified in the database and analysed for major patient characteristics, pre-treatment aspects, and major clinical endpoints. Kaplan Meier estimates were used to calculate overall survival (OS) and progression-free survival (PFS), whereas cumulative incidence was used for relapse incidence (RI), and non-relapse mortality (NRM). Results: 74 pts with PCNSL (n = 10) or SCNSL (n = 64) and complete information on major endpoints after CART and a median follow-up of 20.2 months [CI: 13.25–23.5] were analysed. Median age was 61.6 years (range 31–80), 31 pts were female. 37 of 57 pts (64.9%) had three or more prior treatment lines, 36.5% of pts had undergone autologous hematopoietic cell transplantation. 14 of 70 pts (20%) had ECOG ≥2. Disease-status at CART was complete (CR) or partial remission (PR) for 31.5% (6.8% and 24.7%, respectively) of pts, 68.5% of pts were in relapse, refractory, or had progressive disease. For one patient information on disease status was missing. 40 pts received axicabtagene ciloleucel (Yescarta®), 34 pts were treated with tisagenlecleucel (Kymriah®). OS- and PFS-rates at 12 months were 51.1% [CI: 40.2–64.8] and 33.7% [CI: 24.3–46.7] for the whole cohort. RI at 12 months was 59.4% [CI: 46.9–69.8]. NRM was 7% [CI: 2.5–14.5]. OS and PFS for pts in CR/PR were 53.0% [CI: 35.5–79.3] and 42.1% [CI: 25.9–68.7]. For the refractory cohort OS and PFS were 51.7% [CI: 38.7–69.0] and 30.6% [CI: 19.9–46.9], respectively. Conclusion: With a 51% OS-rate at 12 months CART seem to be a very effective therapeutic option in heavily pre-treated r/r PCNSL or SCNSL, particularly for pts being refractory to prior therapy. These results compare favourably with those of conventional treatment (including a minority of pts treated with autoSCT) in SCNSL with a median overall survival of 3.5 months (Schmitz et al., 2016) and 12-months OS-rate of 20% (Thieblemont et al., 2023). Pts with CNS involvement and r/r LBCL should be considered for treatment with CART.