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Risankizumab is a humanized IgG monoclonal antibody inhibitor of IL23 and has been recently approved by the EMA and the FDA for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy. Its efficacy and safety have been reported by clinical trials and real-life studies. However, even if long-term data from trials have already been reported (up to 172 weeks), data on long-term real-life experiences are still limited. The aim of our study was to investigate the long-term (2 years) efficacy and safety of risankizumab for psoriasis management in a real-life setting. A monocentric retrospective study was performed, enrolling 168 patients affected by moderate to severe psoriasis who were undergoing treatment with risankizumab. Psoriasis severity and safety outcomes were evaluated at each follow-up visit (week 16, week 28, week 52, week 88, week 104). A statistically significant reduction of psoriasis severity scores was reported from week 16 and was maintained up to week 104. Moreover, interesting results in terms of safety have been collected, without any serious adverse events registered. Our long-term real-life monocentric retrospective study confirmed the efficacy and safety of risankizumab up to 104 weeks of treatment. However, further studies are required to confirm our results and to increase available data to establish the best evidence-based biologic selection algorithm.