Prader-Willi syndrome (PWS) is the most common form of syndromic obesity associated with hyperphagia. Because ghrelin stimulates gastric motility in rodents, and PWS patients have 3- to 4-fold higher fasting plasma ghrelin concentrations than normal subjects, we hypothesized that hyperphagia associated with PWS may be partly explained by rapid gastric emptying due to the increased gastric motility caused by ghrelin. We determined gastric emptying times (GETs) and measured ghrelin levels in 11 PWS children and 11 age-, sex-, and body mass index-matched controls using a standard meal containing [(99m)Tc]diaminetriaminepentacetate. Median plasma ghrelin levels before (precibum) and after the GET study were higher in PWS patients than in controls (P = 0.004 and P = 0.001, respectively). Median percent gastric retentions at 90 min after the standard meal were 57.1% (range, 34.0-83.2%) in PWS patients and 40.2% (range, 27.2-60.2%) in controls (P = 0.03). In particular, precibum ghrelin concentrations were not significantly correlated with the rate of gastric emptying in PWS patients (P = 0.153; r = 0.461) or controls (P = 0.911; r = 0.048). Our results show that gastric emptying in PWS is reduced despite higher ghrelin levels, and that the voracious appetite associated with PWS is related to another mechanism.