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Background: Confirmatory data on long-term effectiveness and safety of ixekizumb in psoriatic patients from real-world studies are needed. Objectives: The primary aim was to evaluate the 3-year drug survival of ixekizumab in the treatment of patients with moderate-to-severe plaque psoriasis, in a multicenter real-world setting. The secondary aim was to assess the influence of predictive factors on the drug survival of ixekizumab. Methods: A retrospective analysis was performed on a cohort of patients with chronic plaque psoriasis, who received at least one dose of ixekizumab before December 2018. The drug survival analysis was performed, descriptively analyzed using Kaplan-Meier survival curves. Multivariable Cox regression analyses were carried out including variables considered of clinical importance. Results: A total of 306 patients was enrolled. The overall drug survival at 12, 24 and 36 months of treatment with ixekizumab was 92.11%, 83.85% and 80.19%, respectively. A higher probability (HR 2.34) of drug withdrawal was found among patients who had already received an anti-IL-17 agent compared with bio-naive patients (p 0.017). Conclusions: We found that ixekizumab is a biological agent characterized by a long term effectiveness, not influenced by several clinical factors and associated with a good safety profile.