Context: Weight-based growth hormone (GH) dosing results in a wide variation in growth response in children with GH deficiency (GHD) or idiopathic short stature (ISS). Objective: The hypothesis tested was whether individualized GH doses, based on variation in GH responsiveness estimated by a prediction model, reduced variability in growth response around a set height target compared with a standardized weight-based dose. Setting: 153 short prepubertal children diagnosed with isolated GHD or ISS (n=43) and >/=1 SDS below mid-parental height standard deviation score(MPHSDS) were included in this 2-year multicenter study. Intervention: The children were randomized to either a standard (43 microg/kg/d) or an individualized GH dose (17-100 microg/kg/d). Main outcome measure: Deviation of HeightSDS from individual MPHSDS (diffMPHSDS). The primary endpoint was difference in the range of 'diffMPHSDS' between the two groups. Results: diffMPHSDS range was reduced by 32% in the individualized-dose group relative to the standard-dose group (p<0.003), whereas the mean 'diffMPHSDS' was equal: -0.42+/-0.46 and -0.48+/-0.67, respectively. Gain in HeightSDS 0-2 yrs was equal for the GH-deficient and the ISS groups; 1.31+/-0.47 and 1.36+/-0.47, respectively, when ISS was classified on the basis of maximum GH peak on the arginine-insulin tolerance test or 24h profile. Conclusion: Individualized GH doses during catch-up growth significantly reduces the proportion of unexpectedly good and poor responders around a predefined individual growth target and results in equal growth responses in children with GHD and ISS.