Background: There is lack of real-world treatment pattern comparison data between ixekizumab and adalimumab which are approved for the treatment of moderate-to-severe plaque psoriasis. Objective: To compare real-world treatment patterns among psoriasis patients initiating ixekizumab or adalimumab in the United States. Methods: Psoriasis patients with ≥1 claim for ixekizumab or adalimumab between March 1, 2016, and May 31, 2018, were identified (index date = date of first ixekizumab or adalimumab claim) from the IBM Watson Health MarketScan ® databases. Patients were required to be continuously enrolled for ≥12 months before the index date and followed for a minimum of 6 months until inpatient death, enrollment end, or study end, whichever occurred first. Treatment persistence, adherence, discontinuation, restart, and switching were analyzed. Inverse probability of treatment weighting and multivariable regression modeling were employed to address cohort imbalances and estimate the adjusted risk of non-persistence, discontinuation, and switching, and the odds of adherence. Results: A total of 646 ixekizumab and 3668 adalimumab users were included and followed for a mean of 14.0 and 16.5 months, respectively. Compared to adalimumab, ixekizumab was associated with 19% lower risk of non-persistence (hazard ratio [HR]=0.81, 95% confidence interval [CI]: 0.69-0.95), 26% lower risk of discontinuation (HR=0.74, 95% CI: 0.62-0.88), and 28% lower risk of switching (HR=0.72, 95% CI: 0.57-0.91). Ixekizumab users had higher odds of medication possession ratio ≥80% (odds ratio [OR]=1.36, 95% CI: 1.10-1.69) but similar odds by proportion of days covered ≥80% (OR=1.22, 95% CI: 0.98-1.53). Conclusion: Psoriasis patients treated with ixekizumab demonstrated longer persistency, higher adherence and were less likely to discontinue or switch treatment compared to adalimumab users. However, while patients achieving highly adherent threshold significantly differed by MPR ≥80%, it did not by PDC ≥80%; hence, further analysis using fixed-length follow-up is required.