Objectives: Noonan syndrome (NS) is characterized by short stature, distinctive facial dysmorphic features, congenital heart defects, skeletal anomalies and webbing of the neck. Growth in NS has been a subject of interest. In the present study, we assessed growth response following GH therapy in prepubertal NS patients harboring different genetic mutations Methods: Among 38 NS patients 23 prepubertal NS patients were enrolled in the study. We assessed growth response following GH therapy among the four genetic groups including 7 patients with PTPN11 positive-mutation group, 11 with PTPN11 negative-mutation group, 3 with RAF1 mutation group, and 2 with SOS1 mutation group. We also evaluated the safety of rhGH therapy in NS patients. Results: Chronologic age of four groups at the start of treatment were 5.1±3.6, 7.1±1.5, 4.0±1.8, 4.0 ±2.7 years, respectively. At the beginning of rhGH treatment, height and growth rate were not statistically different depending on different groups. During the three years of rhGH therapy, patients with PTPN11 negative mutation showed more improvement in height (from −2.163 SDS to −0.413 SDS, p=0.002) and growth rate (from 5.15±0.95cm to 7.86±1.17cm, p 0.0001) compared to other groups ( PTPN11 positive-mutation group; from −2.26 SDS to −1.21 SDS, p=0.075, from 5.5±2.1cm to 6.6±0.9cm, p=0.220, RAF1 mutation group; from −3.87 SDS to −1.05 SDS, p=0.099, from 5.9±1.6cm to 8.6±1.6cm, p=0.110, SOS1 mutation group; from −4.07 SDS to −2.45 SDS, p=0.628, from 5.5±0.7cm to 8.4±0.5cm, p=0.05). Serum IGF-1 SDS levels of PTPN11 positive-mutation group were elevated from -0.907±1.250 to 0.779±1.586 (p=0.011). During the three years of rhGH therapy, regular cardiological and haematological check-ups were performed, leading to the conclusion that rhGH therapy was safe even in RAF1 mutation group. Conclusions: Three-year response to growth hormone in pre-pubertal NS children is various depending on disease-causing genetic type. Furthermore, despite small number of patients, the therapy appeared to be safe since no severe adverse effects were reported, at least during the three years.