Introduction <p>Minimal disease activity (MDA) has recently been introduced as comprehensive treatment target in atopic dermatitis (AD), integrating both clinician- and patient-reported outcomes. Evidence on the real-world feasibility and impact of achieving MDA on quality of life (QoL) remains limited. This analysis evaluated the association between MDA achievement and QoL outcomes in patients with moderate-to-severe AD receiving upadacitinib (UPA) in real-world clinical practice.</p> Methods <p>This interim analysis used data from the ongoing, prospective, multicenter, non-interventional UP-TAINED study (NCT05139836) in Germany. Analyses included all patients without treatment interruptions during the first 12&#xa0;months (<i>n</i> = 259). Disease control was classified as optimal, moderate, or none. Optimal control (MDA) was defined as Eczema Area and Severity Index (EASI) ≤ 3 and Worst Pruritus Numeric Rating Scale (WP-NRS) ≤ 0/1; moderate control as EASI ≤ 3 with WP-NRS 2–3 or EASI &gt; 3–7 with WP-NRS ≤ 3; and no control as EASI &gt; 7 or WP-NRS &gt; 3. QoL outcomes were assessed using validated patient-reported measures.</p> Results <p>MDA was achieved by 38.2% of patients at month&#xa0;1 and by 42.1% at month&#xa0;12. Those achieving MDA reported substantially greater improvements across all QoL measures compared with patients with moderate or no disease control. QoL outcomes were comparable between patients starting UPA at 15&#xa0;mg or 30&#xa0;mg. The most frequent adverse events were AD, acne, and corona virus disease 2019 (COVID-19) infection; the safety profile was consistent and no new safety signals were identified.</p> Conclusion <p>Achieving MDA was associated with markedly improved QoL in real-world AD management, supporting MDA as a feasible and clinically meaningful treatment goal in routine practice.</p> Trial Registration <p>ClinicalTrials.gov Identifier, NCT05139836.</p>