Background: Delandistrogene moxeparvovec, a recombinant AAV vector-based gene therapy, is approved in the USA and other select countries. EMBARK (NCT05096221), a two-part Phase 3 study, assessed delandistrogene moxeparvovec safety and efficacy in ambulatory patients with Duchenne muscular dystrophy (DMD) aged ≥4–<8 years. Caregivers reported tangible improvements in disease status 1 year post-delandistrogene moxeparvovec infusion versus placebo, specifically DMD symptoms, physical ability, ability to perform daily activities, and overall health, assessed using the Caregiver Global Impression of Change (CaGI-C) scale. Two-year results are presented. Methods: CaGI-C scores at Weeks 52 (Part 1) and 104 (Part 2) were assessed in participants who received delandistrogene moxeparvovec in Part 1 and in participants who received placebo in Part 1 before crossing over to delandistrogene moxeparvovec in Part 2. Responses were categorized as improvement, no change, or worsening (relative to study start). Comparisons were assessed using multidomain responder index and ordinal regression analyses. Results: In Part 1 delandistrogene moxeparvovec-treated participants, CaGI-C scores (n=56) across all domains indicated persistent and stabilized benefits between Weeks 52 and 104 (difference: −0.1; 95% confidence interval [CI] 0.6–0.4; P=0.61). For Part 2 delandistrogene moxeparvovec-treated participants, when comparing CaGI-C scores at Week 104 (52 weeks post-dose) versus Week 52 (placebo in Part 1), caregivers (n=52) reported nominally significant improvements (difference: 1.5; 95% CI 0.6–2.4; P<0.001). No significant differences were observed when comparing Week 104 data (all items) of participants receiving delandistrogene moxeparvovec in Part 1 versus Part 2 (odds ratio 1.0–1.6; 95% CIs included one). Conclusions: At 2 years post-delandistrogene moxeparvovec infusion, caregivers reported maintenance of clinical improvements reported at 1 year post-infusion. Consistency in caregiver-reported improvements were observed for participants treated with delandistrogene moxeparvovec in Part 1 and Part 2. Parental perceptions provide insights beyond clinician-reported and performance-based outcomes, offering a complementary perspective on treatment impact.