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Biological targeted therapy serves as a new alternative treatment for psoriasis due to its minimal side effects. This study is aimed at examining the drug effectiveness and safety of risankizumab and ustekinumab for psoriasis treatment, so as to provide a reference for clinical decision-making. Databases from Embase, Web of Science, PubMed, and Cochrane Library were gathered, starting from inception to March 1, 2022, for randomized controlled trials regarding risankizumab and ustekinumab for psoriasis treatment. All retrieved articles were carefully selected in strict accordance with a set of inclusion and exclusion criteria. Stata 15.0 and RevMan 5.4 were applied to perform meta-analysis and risk of bias assessment. A total of two trials with three NCTs were selected, with 384 participants in the risankizumab group and 140 participants in ustekinumab. Meta-analysis showed that in the long-term and short-term PASI100, risankizumab was more effective than ustekinumab (RR = 2.27, 95% CI (1.77, 2.90), p < 0.05; RR = 2.33, 95% CI (1.75, 3.08), p < 0.05). In PASI90, RR = 1.77, 95% CI (1.54, 2.03), and p < 0.05 and RR = 1.72, 95% CI (1.48, 2.00), and p < 0.05. In short-term PASI75, RR = 1.23, 95% CI (1.13, 1.34), and p < 0.05. In sPGA of 0, the results at week-16 and week-52 showed that risankizumab was significantly more effective than ustekinumab (RR = 2.24, 95% CI (1.67, 3.01), p < 0.05; RR = 2.30, 95% CI (1.80, 2.95), p < 0.05). Risankizumab was significantly more effective than ustekinumab in improving the quality of life and PSS scores (RR = 1.48, 95% CI (1.26, 1.75), p < 0.05; RR = 2.01, 95% CI (1.41, 2.85), p < 0.05). Nevertheless, risankizumab and ustekinumab did not show significant difference in the incidence of adverse responses (RR = 1.02, 95% CI (0.75, 1.39), p > 0.05). Risankizumab was more effective than ustekinumab for the treatment of psoriasis. The adverse reactions of both risankizumab and ustekinumab were similar and could be tolerated. Risankizumab might be a better alternative option for their treatment. [ABSTRACT FROM AUTHOR]