This is a long-term retrospective multicenter study on adult patients with moderate to severe psoriasis in order to assess long-term efficacy and safety of ixekizumab in a real-world setting. Our observation took into account all patients who started treatment between July 1, 2017 and December 31, 2019 maintaining the treatment for at least 4 years. The majority of our cohort (52 patients; 74.3%) was between 260 and 312 weeks (6 years) under continuous treatment with ixekizumab. Our data confirm that ixekizumab may be considered a long-term effective and safe therapeutic option of moderate to severe plaque psoriasis.