Abstract Introduction/Background Atopic dermatitis (AD) affects approximately 5-10% of adults worldwide, significantly burdening affected patients. Newer treatments for moderate-to-severe AD, including biologic therapies and Janus-kinase (JAK) inhibitors, are associated with varied levels of efficacy, safety, monitoring, and administration requirements. Yet, patient preferences for different treatment options are not well characterized. Objectives A discrete choice experiment (DCE) was designed to quantify the extent to which AD patients in the United States (US) value different treatment attributes. Methods An online DCE survey was conducted in June 2023. Eligible participants included US adults (≥ 18 years) with self-reported moderate-to-severe AD or experience with systemic therapy, diagnosed with AD for ≥1 year, with inadequate response to topical treatments. DCE attributes were selected based on qualitative interviews with patients and clinical input, including attributes related to efficacy (i.e., sustained improvement in skin appearance, itch control), safety (i.e., risk of respiratory infection, cancer, and heart problems), treatment administration, and blood test frequency. Participants were presented 12 choice tasks, each presenting two hypothetical treatment profiles, and selected one profile from each task that reflected their preferred option. A conditional logit regression model was used to assess patient preferences for attributes. Sensitivity analyses were conducted, excluding patients who failed validity tests. Results A diverse group of 300 participants completed the survey (mean age: 45 years; 22% non-white or mixed; 70% female; 66% employed). Approximately half received their first AD treatment of any kind 5 or more years ago (50%), had experienced severe symptoms (50%), and had experience with systemic therapy (52%). Participants preferred treatments with higher efficacy, lower risk of AEs, and less frequent blood tests (p < 0.05). Frequency and mode of administration (i.e., oral vs. injectable) did not impact preferences (p > 0.05). On average, participants were willing to accept a reduction of 35.4, 17.7, and 1.2 percentage points in the probability of achieving itch control to receive a treatment with 1 percentage point less risk of cancer, heart problems, and respiratory infections, respectively. Treatment attributes, from high to low relative importance, were itch control (38%), followed by risk of cancer (23%), risk of respiratory infections (18%), risk of heart problems (11%), sustained improvement in skin appearance (5%), blood test frequency (3%), and frequency and mode of administration (2%). Results were similar in sensitivity analyses, indicating the robustness of the findings. Conclusions Patients with moderate-to-severe AD preferred treatments that maximize itch control while minimizing the risk of AEs (cancer, respiratory infections, heart problems), whereas mode of administration had little impact on preferences. Understanding patients’ preferences may help improve shared decision-making.