CONTEXT: Individuals with Prader-Willi syndrome (PWS) have a high cardiovascular risk, the mechanism of which is unclear. There may be dysfunction in the autonomic nervous system (ANS) in PWS. OBJECTIVE: To measure, as indicators of cardiac autonomic function, postprandial heart rate variability (HRV) and arterial stiffness in adults with PWS. METHODS: Ten adults with PWS were compared with 11 matched healthy obese subjects and 9 healthy lean subjects. Electrocardiographic traces and arterial stiffness were recorded over a period of 10 minutes at -60, 0, 30, 60, 120 and 240 minutes after consumption of a standardized 600-kCal breakfast. Frequency domain analysis was performed using fast Fourier transform to estimate power spectral density in the full spectrum and in low-frequency (LF 0.04-0.15 Hz) and high-frequency (HF 0.15-0.40 Hz) bands. RESULTS: ANCOVA revealed a reduced LF HRV meal response in adults with PWS compared with obese controls, with no differences in HF HRV, LF/HF ratio, heart rate, total power or arterial stiffness meal responses. CONCLUSIONS: This study assessed cardiac autonomic function in adults with PWS compared with matched obese and lean subjects in response to a meal. Results suggest impaired postprandial ANS responsiveness in PWS, which could contribute to both the known increased cardiovascular risk and obesity.