Current clinical recommendations for Duchenne muscular dystrophy (DMD) emphasize the importance of early diagnosis and treatment. Study 4658-102 (NCT03218995) demonstrated the safety and tolerability of eteplirsen in the youngest population of patients with DMD (6 to 48 months) in a clinical trial. Here, patients’ (<84 months old) experience with phosphorodiamidate morpholino oligomer (PMO) treatment (eteplirsen, golodirsen, or casimersen) in routine clinical practice is described for the first time from the ongoing phase 4, observational, EVOLVE study. Methods Patients were stratified by age at PMO treatment initiation: <24, 24 to <48, and 48 to <84 months. The interim analysis included steroid use, treatment duration, safety, and loss of ambulation. Results As of December 2021, 32 patients <84 months were enrolled; eteplirsen-treated (n=30): mean (SD) age (years) at treatment initiation was 1.8 (0.05), 3.3 (0.42), and 5.7 (0.74), and mean (SD) treatment duration (years) was 2.5 (1.45), 2.8 (1.66), and 4.6 (1.54) for the <24, 24 to <48, and 48 to <84-month-old groups, respectively. Steroid usage before eteplirsen initiation was 0/3, 1/7 (14%), and 12/20 (60%) for the 3 age groups. Three serious adverse events (SAEs) occurred in 2/30 (6.7%) eteplirsen-treated patients; none were determined to be treatment related. Eteplirsen was well tolerated with no treatment-related discontinuations or treatment interruptions. Two patients, 1 golodirsen-treated and 1 casimersen-treated patient, were enrolled (ages 6.4 and 6.2 at treatment initiation, respectively; treatment duration was 0.7 years for each). Neither had prior steroid use or SAEs reported. Conclusion These real-world data are consistent with the safety of previous clinical studies and add to the body of evidence supporting the early initiation of treatment with PMO therapy in patients <7 years old.