Background: Management of chronic hand eczema (CHE) remains a challenge; effective topical treatment is limited to corticosteroids. Objectives: To assess the efficacy and safety of a novel, pan-Janus kinase inhibitor (delgocitinib) in patients with CHE. Methods: In this randomized, double-blind, phase IIa study, patients with CHE received delgocitinib ointment 30 mg g(-1) or vehicle ointment for 8 weeks. The primary end point was the proportion of patients achieving treatment success ['clear'/'almost clear' skin with ≥ 2-point improvement in the Physician's Global Assessment of disease severity (PGA)] at week 8. Secondary end points included Hand Eczema Severity Index (HECSI) score changes and the proportion of patients achieving treatment success on the Patient's Global Assessment of disease severity (PaGA). Results: Ninety-one patients were randomized. More patients receiving delgocitinib (46%) than vehicle (15%) [odds ratio 4 center dot 89, 95% confidence interval (CI) 1 center dot 49-16 center dot 09; P = 0 center dot 009] achieved treatment success (PGA). Adjusted mean HECSI score at week 8 was lower with delgocitinib (13 center dot 0) than with vehicle (25 center dot 8) (adjusted mean difference -12 center dot 88, 95% CI -21 center dot 47 to -4 center dot 30; P = 0 center dot 003). More patients receiving delgocitinib than vehicle achieved treatment success by PaGA, but this did not reach statistical significance. The incidence of adverse events was similar with delgocitinib and vehicle; none led to discontinuation of delgocitinib. Conclusions: Delgocitinib ointment was efficacious and well tolerated. As a plateau of efficacy was not observed, a longer treatment period may lead to increased efficacy. Further clinical studies are warranted to confirm these findings in patients with CHE.