Background: Eosinophilia is common in patients with atopic dermatitis (AD). Abrocitinib, an oral Janus kinase-1 inhibitor and dupilumab, an anti–interleukin-4 receptor-α antibody, are approved for moderate-to-severe AD. Dupilumab has been associated with transient eosinophilia. Objectives: To assess the effect of abrocitinib and dupilumab on eosinophils in patients from the phase 3 JADE COMPARE (NCT03720470) and JADE EXTEND (NCT03422822) trials. Methods: In JADE COMPARE, patients received once-daily oral abrocitinib (200/100 mg), placebo or subcutaneous dupilumab (300 mg, biweekly) with background topical therapy. In the ongoing long-term JADE EXTEND study (Data cutoff: April 22, 2020), dupilumab-treated patients from JADE COMPARE received once-daily abrocitinib (200/100 mg) with background topical therapy. The proportion of patients with eosinophilia and hypereosinophilia, and association of eosinophilia with clinical efficacy was assessed. Adverse events (AEs) were also assessed. Results: Of the 837 patients in JADE COMPARE, 58 (25.7%), 47 (19.7%) and 51 (21.1%) had eosinophilia at baseline in the abrocitinib 200 mg, abrocitinib 100 mg and dupilumab groups, respectively. At Week 16, eosinophilia decreased with abrocitinib 200 mg (9.3%) and abrocitinib 100 mg (19.0%) but not dupilumab (21.5%); no cases of hypereosinophilia were observed with abrocitinib 200 mg compared with abrocitinib 100 mg (1.9%) and dupilumab (2.3%). Decreases in median eosinophil counts were greater with abrocitinib 200 mg (difference, −100/mm3) and abrocitinib 100 mg (−70/mm3) than dupilumab (+25/mm3) or placebo (+30/mm3) at Week 16. Similar trends were observed in patients with comorbid asthma and allergic rhinitis. Eosinophilia decreased from baseline to Week 12 in dupilumab-treated patients who switched to abrocitinib in JADE EXTEND. Decreased eosinophil counts with abrocitinib correlated positively with improvements in AD severity, itch and sleep loss. No eosinophilia-associated AEs occurred. Conclusions: Abrocitinib decreased eosinophilia in patients with moderate-to-severe AD who had baseline eosinophilia. Resolution of eosinophilia was associated with abrocitinib clinical efficacy. © 2023 The Authors. JEADV Clinical Practice published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.< Réduire