Background: Tralokinumab, a monoclonal antibody that specifically neutralizes interleukin (IL)-13, is approved for the treatment of adults with moderate-to-severe atopic dermatitis (AD). Tralokinumab was studied in ECZTRA3 (NCT03363854), a randomized, double-blind, multi-national, placebo-controlled Phase 3 trial of tralokinumab in adults with moderate-to-severe AD. Objective: We conducted a post-hoc analysis in the United States (US) subset of ECZTRA3 patients to inform healthcare practitioners and payers on the efficacy and safety of tralokinumab in the US setting. Methods: Patients were treated with either 300 mg tralokinumab (n=63) or placebo (n=25) every 2 weeks (Q2W) in combination with TCS as needed for an initial 16 weeks. Thereafter, tralokinumab-treated patients continued with either Q2W dosing or Q4W+TCS for 16 additional weeks. Primary, secondary, and safety endpoints of the ECZTRA3 US subset were evaluated at 16 and 32 weeks following main statistical analyses (previously published). Results: At Week 16, 37.1% tralokinumab+TCS vs 12.0% placebo+TCS reached Investigator’s Global Assessment (IGA) 0/1 (nominal P=0.039); 56.5% of tralokinumab+TCS vs 24.0% placebo+TCS (nominal P=0.012) achieved the Eczema Area and Severity Index (EASI)-75. Secondary, patient-reported outcomes including itch score and health-related quality of life (HRQoL) were also improved at Week 16 versus baseline, more so for tralokinumab+TCS group. Tralokinumab was well tolerated, with an overall safety profile comparable to placebo. Conclusions: Consistent with the full ECZTRA3 population, US patients with moderate-to-severe AD treated with tralokinumab+TCS as needed achieved greater symptom relief, reductions in disease severity and improvement of HRQoL than placebo+TCS, with comparable safety.