Dupilumab, a monoclonal antibody targeting interleukin (IL)-4 and IL-13 pathways, has been established as a first-line biologic therapy for moderate-to-severe atopic dermatitis (AD). However, real-world data in Asian populations remain limited. This study evaluates the long-term effectiveness and safety of dupilumab in Korean adult patients with moderate-to-severe AD. A retrospective observational study was conducted at a South Korean tertiary care hospital between 2018 and 2024. Clinical outcomes including eczema area and severity index (EASI), numerical rating scale (NRS) (pruritus), and dermatology life quality index (DLQI) were analyzed at regular time points up to 232 weeks. Changes in concomitant medication use and adverse events (AEs) were also recorded. Among 128 screened patients, 84 met the inclusion criteria. EASI scores decreased from 27.6 ± 5.5 at baseline to 2.7 ± 1.3 at week 232. EASI-75 was achieved by 100% of patients from week 16 onward, while EASI-90 reached 50% by week 232. Significant improvements were also observed in NRS and DLQI scores. TCS and OAH use significantly declined over time. Most AEs were mild and resolved during continued treatment. Dupilumab demonstrates durable effectiveness and a favorable safety profile in Korean adults with moderate-to-severe AD. These results support its continued use as a long-term systemic therapy in real-world settings.