Ixekizumab (Taltz®) is a humanized anti-IL-17A monoclonal antibody approved for the treatment of various inflammatory diseases including psoriasis and psoriatic arthritis. Despite the favorable efficacy and safety, ixekizumab is also known for its high incidence of injection site reactions (ISRs), ranging from 6% to 55% in different studies according to different definitions and studied population. However, specific risk factors for ixekizumab-induced injection site reactions in patients with psoriatic diseases had not been well studied. In this retrospective study, we found that overweight or obesity might be a protective predictor for the occurrence of ixekizumab-induced ISRs in patients with psoriatic disease. Meanwhile, having a positive family history of psoriasis might be a potential risk factor. Last but not least, patients with diarrhea following ixekizumab injection were associated with a higher risk of developing ISRs. Future high-quality studies with larger samples are warranted to verify the relationship.