HRQOL as a multidimensional construct has not been previously investigated in children with Asperger's Syndrome. The objective of the present study was to examine the initial feasibility, reliability, and validity of the PedsQL 4.0 Generic Core Scales and PedsQL Cognitive Functioning Scale parent proxy-report versions in school-aged children with Asperger's Syndrome. The PedsQL evidenced no missing responses (0.0%), achieved excellent reliability for the Generic Core Total Scale score (alpha = 0.82) and Cognitive Functioning Scale (alpha = 0.92), distinguished between children with Asperger's Syndrome and a matched sample of healthy children, and was related to similar constructs on the Asperger Syndrome Diagnostic Scale. The results demonstrate the initial measurement properties of the PedsQL in school-aged children with Asperger's Syndrome.