Background: The clinical relevance of low IGF-I levels, caused by cranial radiotherapy, in adult childhood cancer survivors has not been studied extensively. We evaluated whether IGF-I is a useful marker for altered body composition and growth hormone deficiency (GHD) in this group. Procedure: We analyzed retrospective data from 610 adult childhood cancer survivors, retrieved from the late effects clinic. Median age at diagnosis was 6 years (interquartile range 3-11) and follow-up time was 18 years (13-24). We assessed IGF-I standard deviation scores (SDS), anthropometrical measures, growth hormone stimulation tests in patients with clinical signs of GHD, and measures of body composition (assessed by dual X-ray absorptiometry, Lunar Prodigy). Results: In 58 cranially irradiated acute leukemia survivors (25 Gy (24-25)) and 56 locally irradiated brain tumor survivors (42 Gy (35-54)) we found significantly lower IGF-I SDS (P<0.001), lower height SDS (P<0.001), higher body mass index (P=0.01), higher waist-hip ratio (WHR; P=0.001), higher total fat percentage SDS (P<0.001), and lower lean body mass SDS (P<0.001), as compared to 452 not cranially irradiated survivors. IGF-I showed a weak inverse correlation with BMI (r=-0.12, P=0.04), WHR (r=-0.15, P=0.01), total fat percentage (r=-0.14, P=0.02), and a positive correlation with lean body mass (r=0.15, P=0.01). In patients with low IGF-I levels, IGF-I did not significantly differ between subjects with and without GHD as determined by GH-stimulation testing (P=0.39). Conclusion: This study shows that IGF-I has limited value as a marker for alterations in body composition in adult childhood cancer survivors. Pediatr Blood Cancer 2012;59:711-716.