Introduction <p>Nonmelanoma skin cancer (NMSC) risk may be increased in patients with immune-mediated inflammatory disorders. Although atopic dermatitis (AD), an inflammatory immune-mediated chronic skin disease, has been associated with the risk of skin cancer, data on the underlying risk of NMSC in patients with AD in the USA are unclear. The objective of this analysis was to evaluate NMSC incidence and risk in patients with AD generally and those with moderate-to-severe disease specifically compared with a non-AD matched control cohort and patients with rheumatoid arthritis (RA).</p> Methods <p>This retrospective observational study examined US claims data (2017–2023) from Optum’s de-identified Clinformatics® Data Mart Database of adults with AD and RA, as well as non-AD control cohorts matched 1:1 to patients with AD and patients with moderate-to-severe&#xa0;AD.</p> Results <p>This analysis included data from 391,753 patients with AD and 97,445 patients with RA. The matched AD and non-AD cohorts each included 381,221 patients. Patients with AD had a higher NMSC incidence rate (cases/100 person-years [95%&#xa0;CI]) than non-AD matched controls (2.12 [2.10, 2.15] vs 1.74 [1.72, 1.77]) and greater relative NMSC risk (adjusted hazard ratio 1.32 [1.30, 1.35]). NMSC incidence and relative risk were similar between patients with AD and RA. Patients with AD were at greater risk of NMSC if they had a history of NMSC, other malignancies, or organ transplantation. Trends were similar among patients with moderate-to-severe disease.</p> Conclusion <p>Patients with AD and those with moderate-to-severe AD had a higher incidence and risk of NMSC than matched individuals without AD.</p>