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The aim of the study was to assess the long‐term effectiveness and safety of secukinumab in Spanish patients with moderate‐to‐severe psoriasis in a daily practice setting. Nationwide multicenter, observational, retrospective, non‐interventional, single‐cohort study including patients who initiated treatment with secukinumab in daily clinical practice conditions. Subjects were followed for a minimum of 3 months and a maximum of 24 months. Psoriasis Area Severity Index (PASI), Body Surface Area and Physician's Global Assessments were collected at baseline and months 3, 6, 12, 18 and 24 during treatment. Adverse events and reasons for secukinumab withdrawal were collected and classified for analyses. A total of 384 patients were enrolled in the study. Median PASI declined rapidly from 14.3 at baseline to 2.7 at month 3, 2.1 at month 12, and remained low (2.8) at month 24. Within the group of patients with PASI ≥10 at baseline (n = 278), 58.3%, 60.4% and 56.5% achieved a PASI90 response at months 3, 12 and 24, respectively. As for absolute PASI, 86.5%, 69.5%, 42.7% and 37% achieved PASI <5, < 3, < 1 and 0, respectively, at month 3. Secukinumab was more effective in biologic‐naïve patients and in those with lower Body Mass Index. Secukinumab presented a good long‐term safety profile. Secukinumab was effective and safe in a routine clinical setting, in a large cohort of patients with moderate‐to‐severe plaque psoriasis, in the short‐, medium‐ and long‐term (up to 24 months). [ABSTRACT FROM AUTHOR]