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Background and Importance Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoproliferative neoplasm among non-Hodgkin lymphomas, characterised by clinical aggressiveness and biological heterogeneity. Autologous Chimeric Antigen Receptor (CAR) T-cell therapies targeting CD19, such as Axicabtagene ciloleucel (axi-cel), have emerged as a promising treatment option. However, evidence on their safety in real-world settings remains limited.Aim and Objectives To evaluate the safety of axi-cel as third-line or later therapy in patients with relapsed/refractory DLBCL.Material and Methods Observational, retrospective, descriptive and multicentre study including patients treated after at least two prior lines of therapy with axi-cel between April2019-May2025. Variables: demographic (age, sex), clinical (disease type, ECOG, transplant previous, treatment line, time to axi-cel infusion from relapse, therapy follow-up) and safety: adverse events (Cytokine Release Syndrome [CRS] and Immune-effector Cell-Associated Neurotoxicity Syndrome [ICANS], stratified according to the American Society for Blood and Marrow Transplantation consensus of 2018; plasma alterations, infections, CMV reactivations, secondary malignancies, mortality).Data were obtained from medical records and prescription systems, and analysed using descriptive statistics.Results A total of 37 patients (mean age 54.1±15.8 years; 59.7% male) were analysed, 83,78% DLBCL, 6 patients with transformed follicular lymphoma. ECOG: 0(35.1%; 13), 1(64.9%; 24). Seven had prior transplants: 5 autologous. Axi-Cel was: 78.4% third-line; 18.9% fourth-line, 2.7% sixth-line. Median of 2.7 months since last relapse. Median therapy follow-up:15.7 (0.4-62.2) months.CRS: 100% (G1:15 patients, G2:18, G3:4), median onset 1 day, duration 5 days; 37.8% required corticosteroids and 73% tocilizumab (median:2; max:4 doses). ICANS:70.3% (G1:6 patients, G2:7, G3:6 y G4:7), median onset 6 days, duration 5 days; treatment: dexamethasone (20 patients), methylprednisolone (6), anakinra (10; median: 7 doses), and siltuximab (2). No tumour lysis or macrophage activation syndromes were seen. ICU admission: 37.8%.Plasma alterations: 13.5% hypofibrinogenemia, and 48.6% hypogammaglobulinemia, with corresponding supportive therapies.Infections: virals (48.6%), bacterials (48.6%), fungals (8.1%), parasitics (2.7%). Notably: COVID-19 (33.3%), CMV reactivation (27.8%), Clostridium difficile (38.9%).Secondary malignancies: 5.4% (therapy-related myelodysplastic syndromes).Mortality: 13 patients (35.1%). Causes:6 progression, 4 early and 3 late complications.Conclusion and Relevance In this real-world cohort, axi-cel showed predictable but significant toxicity, including universal CRS and cytopenias, frequent ICANS and infections, and substantial supportive care needs. These results highlight the importance of close monitoring, multidisciplinary management, and long-term follow-up for patients undergoing CAR-T therapy.Conflict of Interest No conflict of interest