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Introduction: Despite Tocilizumab is now recognized as a concrete therapeutic option in patients with severe SARS-CoV-2 related respiratory failure, literature lacks about factors influencing the response to it in this context. Therefore, the aim of our study was to provide evidence about predictors of poor outcome in Tocilizumab treated patients in the real-world practice., Materials and Methods: We retrospectively analyzed clinical, laboratory and chest computer tomography (CCT) data of patients firstly admitted in non Intensive Care Units (ICU) and suffering from severe respiratory failure, who were treated with the IL-6 antagonist Tocilizumab. We compared patients who died and/or required admission to ICU with oro-tracheal intubation (OTI) with those who did not., Results: Two hundreds and eighty-seven patients (29.9% females) with mean age ± SD 64.1 ± 12.6 years were the study population. In-hospital mortality was 18.8%, while the composite endpoint in-hospital mortality and/or ICU admission with OTI occurred in 23.7%. At univariate analysis, patients who died and/or were admitted to ICU with OTI were significantly older and co-morbid, had significantly higher values of creatinine, C-reactive protein (CRP) and procalcitonin and lower lymphocytes count, PaO2/FiO2 ratio (P/F) and room air pulsossimetry oxygen saturation (RAO 2 S) at hospital admission. Computed tomography ground glass opacities (CT-GGO) involving the pulmonary surface ≥ 50% were found in 55.4% of patients who died and/or were admitted to ICU with OTI and in 21.5% of patients who did not (p=0.0001). At multivariate analysis, age ≥ 65 years (OR 17.3, 95% CI: 3.7-81.0), procalcitonin ≥ 0.14 (OR 9.9, 95%CI: 1.7-56.1), RAO 2 S ≤ 90% (OR 4.6, 95%CI: 1.2-17.0) and CCT-GGO involvement ≥ 50% (OR 5.1, 95%CI: 1.2-21.0) were independent risk factors associated with death and/or ICU admission with OTI., Conclusion: Tocilizumab has shown to improve outcome in patients with severe respiratory failure associated to SARS-CoV-2 related pneumonia. In our multicentre study focusing on Tocilizumab treated severe COVID-19 patients, age ≥ 65 years, procalcitonin ≥ 0.14 ng/mL, RAO 2 S ≤ 90% and CCT-GGO involvement ≥ 50% were independent factors associated with poor outcome., (Copyright © 2022 Elsevier B.V. All rights reserved.)