To determine the effect of method of growth hormone (GH) administration on patient outcomes, we studied data from the GHMonitor, an electronic database registry of North American children treated with Saizen GH (somatropin [rDNA origin] for injection). Data from 631 children, 305 treated with needle and syringe and 326 treated with cool.click needle-free device, were analyzed. The groups were balanced for factors known to affect GH treatment response. There was no difference in response to GH over 2 years of treatment whether assessed by growth rate, change in height SD score, or change in height age. Although the majority of patients were compliant with GH therapy (84.6% of needle-free delivery system [NFDS] and 76.3% of needle and syringe patients missed <3 doses per month), significantly more patients using needle and syringe missed over one-half of their prescribed GH dose (13.4% needle and syringe patients versus 6% of NFDS patients, P=.002). In this group of poorly compliant patients, growth rates were significantly lower than in patients who missed fewer doses. Thus in patients where compliance is an issue, use of the NFDS may result in better outcomes.