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Abstract Background The oral anti‐janus kinase 1 inhibitor upadacitinib has shown a good efficacy–safety profile in the treatment of moderate‐to‐severe atopic dermatitis (AD) in clinical trials; however, few data from real clinical practice have been published so far. Objectives To evaluate the efficacy and safety of upadactinib in clinical practice. Methods An observational and multicentric study was conducted. Inclusion criteria consisted of patients who had previously received upadacitinib in the clinical trial M19‐850 and continued treatment with upadacitinib (15 mg or 30 mg) under daily clinical practice conditions for 12 months. Demographic data, characteristics of AD, treatment response and adverse events were recorded. Preliminary results at 24‐week follow‐up are herein presented. Results A total of 26 patients (61.54% males, mean age: 35.58 years) were included in the study; of these, 92.31% received upadacitinib 30 mg at baseline. At 24 weeks, mean values of Eczema Area and Severity Index and body surface area were 2.26 and 2.37%, respectively, 82.35% of the patients reached the Investigator's Global Assessment 0/1 and the mean value of peak pruritus numerical rating scale was 1.74. Adverse events were present in 19.23% of the cases, causing one definitive treatment interruption (due to herpes zoster) and two temporary treatment discontinuations (due to temporary elevation of creatine kinase). Conclusions These data support the maintenance of the efficacy of upadacitinib at 24‐week posttrial follow‐up, with no unexpected safety concerns. More real‐world data are needed to confirm these results.