A comparison of real-world treatment patterns of ixekizumab (IXE)-treated and adalimumab (ADA)-treated psoriasis patients in the United States over 24 months. The IBM Watson Health MarketScan® databases were used in the study. Adult psoriasis patients with≥ 1 claim for IXE or ADA were identified. Inverse probability of treatment weighting (IPTW) was used to address cohort imbalances. The risks of non-persistence, discontinuation and switching were estimated using Cox proportional hazards models. The odds of high adherence were estimated using logistic regression. The persistence, adherence, discontinuation, reinitiation, and dosing and switching rates were also investigated. Over 24 months, it included 475 IXE users and 3,159 ADA users. When compared to ADA users, IXE users demonstrated higher adherence (36.3% vs 28.8% ; P<0.001) and persistence rates (35.2% vs 28.8% ; P=0.004), as well as a lower discontinuation rate (59.1% vs 65.3%; P=0.007). When compared to ADA users, IXE users had a higher likelihood of treatment adherence (OR=1.52, 95% CI: 1.24–1.87), a lower risk of non-persistence (HR=0.84, 95% CI: 0.75–0.95), and a lower risk of discontinuation (HR=0.83, 95% CI: 0.74–0.94). Both groups’ switching rates were comparable (31.2 vs. 30.0%; P=0.608). Over 24 months, IXE users had better treatment adherence and persistence and a lower risk of discontinuation compared to ADA users, with no risk of switching between the two.