Mental retardation is one of the clinical characteristics of Prader-Willi syndrome (PWS) and in part of the patients growth hormone deficiency is demonstrable. Cognitive function seems to be influenced by insulin-like growth factor I (IGF-I); however, little is known about cognitive function in relation to IGF-I levels in PWS adults. The aim of the present study was to evaluate cognitive function in adult PWS patients in comparison to healthy siblings and to investigate whether there is a correlation between cognitive function and IGF-I levels. Anthropometric measurements, IGF-I levels, quality of life (QoL), Appetite Assessment Score, IQ (GIT and Raven) and cognitive function (by four subtests of the Cambridge Neuropsychological Automated Testing Battery, CANTAB) were evaluated in PWS patients and their healthy siblings served as control group. PWS patients had significantly lower IGF-I levels, IQ and QoL when compared to controls. Reaction times were longer and performance was worse on CANTAB subtests in PWS adults. IGF-I on one hand and IQ, Appetite Assessment Score and cognitive performance on the other hand seem to be correlated in PWS patients. In conclusion, IGF-I levels, IQ and QoL are significantly lower in PWS subjects when compared to healthy siblings. In PWS adults, temporal as well as prefrontal cognitive functions are impaired. Higher IGF-I levels appear to be related to better intellectual skills and faster temporal memory processing in PWS patients. © 2011 Elsevier Inc.