OBJECTIVE Prader-Willi syndrome (PWS), the leading known genetic cause of obesity, is characterized by intellectual disabilities, maladaptive and compulsive behaviors, and hyperphagia. Although complications of obesity resulting from hyperphagia are the leading cause of death in PWS, quantifying this drive for food has long been an unmet research need. This study provides factor-analytic and within-syndrome analyses of a new measure of hyperphagia in PWS. METHODS A 13-item informant measure, the Hyperphagia Questionnaire, was developed and administered to the parents of 153 persons with PWS, 4 to 51 years of age. The intelligence quotients, genetic subtypes of PWS, and BMIs of offspring were obtained, as were measures of their non-food problem behaviors. RESULTS Factor analyses with varimax rotation produced three statistically and conceptually robust factors that accounted for 59% of the variance: Hyperphagic Behaviors, Drive, and Severity. Hyperphagic Behavior increased with age, whereas Drive remained stable, and Severity dipped in older adults. Hyperphagic Drive and Severity were positively correlated with non-food behavior problems, and Hyperphagic Drive differentiated the 36% of participants with extreme obesity from those who had overweight/obese (48%) or healthy (16%) BMI classifications. CONCLUSIONS The Hyperphagia Questionnaire is a robust tool for relating breakthroughs in the neurobiology of hyperphagia to in vivo food-seeking behavior and for examining the psychological and developmental correlates of hyperphagia in PWS. The Hyperphagia Questionnaire also offers a nuanced, real-life outcome measure for future clinical trials aimed at curbing the life-threatening drive for food in PWS.