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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 in PWS. OBJECTIVE: To measure, as indicators of cardiac autonomic function, postprandial heart rate variability (HRV) and arterial stiffness in adults with PWS. METHODS: 10 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 standardised 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 analysis revealed a reduced low-frequency (LF) HRV meal response in PWS compared to obese controls, with no differences in high-frequency (HF) HRV, LF/HF ratio, heart rate, total power or arterial stiffness meal responses. CONCLUSIONS: The current study assesses cardiac autonomic function in PWS compared with matched obese and lean in response to a meal. Results suggest impaired postprandial autonomic nervous system responsiveness in PWS, which could contribute to both the known increased cardiovascular risk and obesity. © 2012 Blackwell Publishing Ltd.