BACKGROUND Turner syndrome (TS) affects more than 50,000 girls and women in the United States. The National Cooperative Growth Study (NCGS) has collected efficacy and safety data for 5220 TS children treated with recombinant human GH (rhGH) during the last 20 yr. OBJECTIVE Our objective was to determine frequencies of specific targeted adverse events (AEs) and additional AEs of interest in TS patients. Corresponding safety data in non-TS patients or normal populations were compared for selected AEs. METHODS Patients may be enrolled at rhGH initiation and followed until discontinuation. Investigators submit AE reports describing any event that is potentially rhGH related or is a targeted event. RESULTS The Genentech Drug Safety department received 442 AE reports for TS NCGS patients as of June 30, 2006, including 117 serious AEs. Seven deaths occurred; five resulted from aortic dissections/ruptures. The incidence of certain events known to be associated with rhGH (targeted events), including intracranial hypertension, slipped capital femoral epiphysis, scoliosis, and pancreatitis, was increased compared with other non-TS patients in NCGS. There were 10 new-onset malignancies that occurred, including six in patients without known risk factors. Type 1 diabetes also appeared to be increased compared with other NCGS groups. CONCLUSIONS Children with TS who were treated with rhGH exhibit an increased underlying risk for selected AEs associated with rhGH and for type 1 diabetes, which is likely unrelated to rhGH. The aortic dissection/rupture incidence reflects the higher baseline risk for these events in TS, was consistent with current epidemiological data in smaller TS populations, and is likely unrelated to rhGH. It is not known whether the reported malignancies represent an inherently increased risk in TS patients. Twenty years of experience in 5220 patients indicates no new rhGH-related safety signals in the TS population. The NCGS and similar registries, although focused on the years during rhGH treatment, may also be a window into the natural history of TS in childhood.