Abstract Context The lack of a severity definition and standardized GH cutoff level for GH deficiency (GHD) diagnosis in children leads to ambiguity in the interpretation of GH stimulation tests and treatment recommendations. Objective To investigate treatment response differences among children with GHD treated with daily GH (somatropin) (year 1) or once-weekly somapacitan (years 1 and 2) based on GH peak concentrations assessed at diagnosis. Methods This was a subgroup analysis of 200 patients with GHD aged ≥2.5 years participating in the REAL4 randomized, phase 3 trial. Height velocity (HV; cm/year) and changes in height SD score (SDS) and IGF-I SDS from baseline were compared for 3 GH peak groups: ≤ 3, >3 to <7, and ≥7 to ≤10 μg/L. Results The ≤3 μg/L GH peak concentration group had the greatest HV at weeks 52 and 104. Mean change in height SDS ranged from 1.89 to 1.59, 1.17 to 1.06, and 0.92 to 1.07 at week 52 and 2.79 to 2.30, 1.64 to 1.54, and 1.33 to 1.51 at week 104 for the 2 treatment groups across the 3 GH peak concentrations, respectively. Mean change in IGF-I SDS ranged from 3.13 to 3.01, 2.11 to 1.96, and 1.87 to 2.26 at week 52 and from 2.81 to 2.11, 1.85 to 1.62, and 1.28 to 1.71 at week 104 for the 3 GH peak concentrations. Conclusion Patients with GHD in the ≤3 μg/L GH peak concentration group had greater HV and greater changes in height SDS and IGF-I SDS from baseline.