Noonan syndrome (NS) is a heterogeneous genetic disorder characterized by short stature. The National Cooperative Growth Study (NCGS), a postmarketing observational study of recombinant human GH (rhGH)-treated children, includes a large cohort of children with NS. We studied NCGS-enrolled prepubertal and pubertal children with NS. Baseline characteristics and growth responses in NS patients with reported near-adult height (NAH) (n = 65) were compared to patients with idiopathic GH deficiency (n = 3007) and Turner syndrome (TS; n = 1378) with reported NAH to identify factors contributing to NAH optimization in NS. NS patients (mean enrollment age, 11.6 yr) received rhGH (mean, 0.33 mg/kg . wk) for a mean of 5.6 yr. No significant difference was observed in Delta height sd score (SDS) between NS (+1.4 +/- 0.7) and TS (+1.2 +/- 0.9). However, Delta height SDS for NS and TS differed significantly from idiopathic GH deficiency (+1.7 +/- 1.0) (P < 0.0001). Mean gain in NAH above projected was 10.9 +/- 4.9 cm (males) and 9.2 +/- 4.0 cm (females). Duration of prepubertal rhGH was an important contributor to prepubertal change in height SDS (r(2) = 0.97). Height SDS at pubertal onset highly correlated with NAH SDS (rho = 0.783; P < 0.0001). Duration of puberty highly correlated with pubertal height gain in centimeters for males (rho = 0.941) and females (rho = 0.882) (P < 0.01). No new adverse events were observed. rhGH significantly improved height SDS for children with NS at NAH. Duration of prepubertal rhGH and height SDS at puberty were important contributors to NAH. Because starting age of the patients in this report was 11.6 yr, these data suggest that greater growth optimization is possible with earlier initiation of therapy.