Atopic dermatitis (AD) profoundly affects quality of life (QoL). Dupilumab significantly improves clinical outcomes, is well tolerated, and approved to treat inadequately controlled moderate-to-severe AD in adults; however, its effect on patient-reported outcomes (PROs) is not fully characterized. To evaluate the impact of dupilumab on patient-reported AD symptoms and QoL. Pooled data were analyzed from two identically designed phase 3 studies, LIBERTY AD SOLO 1 (NCT02277743) and SOLO 2 (NCT02277769), assessing the following PROs: Peak Pruritus Numerical Rating Scale (NRS), Pruritus Categorical Scale, SCORing AD (SCORAD), Dermatology Life Quality Index (DLQI), Patient-Oriented Eczema Measure (POEM), Hospital Anxiety and Depression Scale (HADS), five-dimension EuroQoL questionnaire (EQ-5D), and patient-assessed disease status and treatment effectiveness. Dupilumab rapidly improved (vs. placebo) Peak Pruritus NRS scores by day 2 ( < .05), anxiety and depression (HADS), and QoL (DLQI) by week 2, and maintained through week 16 ( < .0001). At week 16, more dupilumab-treated than placebo-treated patients reported improvement in SCORAD itch and sleep, and no pain/discomfort (EQ-5D) ( < .0001). Cultural differences of translated PROs. Dupilumab had a significant, positive impact on AD symptoms, including itch, sleep, pain, anxiety and depression, and QoL in adults with moderate-to-severe AD.