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Dupilumab is a monoclonal antibody approved for the treatment of moderate-to-severe atopic dermatitis (AD) in patients aged ≥12years. Large, double-blind, randomised, placebo-controlled trials showed its efficacy and safety in adolescents. However, real-life data are few. The aim of this monocentric retrospective observational study (December 2020-November 2021) was to assess the effectiveness and safety of dupilumab in AD adolescents treated for at least 24 weeks. For each patient demographic features, clinical data and adverse events (AEs) were collected. Eczema Area and Severity Index (EASI), Numerical Rating Scale (NRS) for pruritus (P-NRS) and for sleep disturbances (S-NRS), and Children Dermatology Life Quality Index (cDLQI) were assessed at baseline, week (W)4, W16, and W24. Twenty-seven patients (18males; 15.23±3.54years) were enrolled. Dupilumab was administered subcutaneously at dosage of 600mg induction dose, followed by 300mg every 2weeks in 14 (51.85%) patients with a weight ≥60kg, while 13 (48.15%) patients with a weight <60kg were treated with dupilumab 200mg every 2weeks after a loading dose of 400mg. The mean EASI score at baseline was 26.96±4.93 and significantly reduced to 3.74±3.47 at W16 (<.001), and to 3.4±5.04 at W24 (p<.001). P-NRS [9.14±0.94 at baseline vs 2.33±4.93 at W16 (p<.001), and 1.45±2.35 at W24 (p<.001)], S-NRS [7.88 ± 1.64 at baseline vs 0.92 ± 1.35 at W16 (p<.001), and 1.66±2.84 at W24 (p<.0001)] and cDLQI [26.62±4.45 vs 2.18±3.51at baseline vs 2.18±3.51 at W16 (p<.001), and 3.4±5.02 at W24 (p<.001)] showed a statistically significative improvement as well. Injection-site reaction (5/27; 18.52%), conjunctivitis (2/27; 7.41%) and asthenia (2/27; 7.41%) were the main AEs collected. This study seems to confirm the efficacy and safety of dupilumab in adolescents with moderate-to-severe AD also in real-life setting. This article is protected by copyright. All rights reserved.