Background: Previous studies showed the potential effectiveness of delgocitinib ointment, a novel topical JAK inhibitor, in atopic dermatitis (AD). Objective: This study aimed to evaluate the efficacy and safety of delgocitinib 0.5% ointment in a 4-week double-blind period (part 1) and in a 24-week extension period (part 2). Methods: In the part 1, Japanese patients aged ≥ 16 years with moderate or severe AD were randomized in a 2:1 ratio to delgocitinib 0.5% ointment or the vehicle ointment. Eligible patients entered the part 2 to receive delgocitinib 0.5% ointment. Results: At the end of treatment in the part 1, the least-squares mean percentage changes from baseline in the modified Eczema Area and Severity Index (mEASI) score, the primary efficacy endpoint, were significantly greater in the delgocitinib group than in the vehicle group (–44.3% vs. 1.7%, P < .001). The improvement in the mEASI score was maintained in the part 2. Most adverse events were mild and unrelated to delgocitinib across the study periods. Limitations: The present study was conducted in Japanese patients only. Conclusion: Delgocitinib ointment was effective and well tolerated when administered to Japanese adult patients with moderate-to-severe AD for up to 28 weeks.