Background: The present authors aimed (a) to objectively quantify spontaneous physical activity (PA) in adult patients with Prader-Willi syndrome (PWS) and (b) to evaluate the transferability of a home-based exercise training programme in these patients. Method: Physical activity was compared between 10 adult women with PWS (PWS group) and 20 adult women with non-syndromic obesity (CON group, for cross-sectional comparison). In the PWS group, PA, body composition, walking capacity, quality of life and eating behaviour were then compared before and after a 16-week supervised exercise programme. Results: The PWS group displayed lower PA and higher sedentary time compared to the CON group. Median attendance to exercise sessions reached 100% (Q1-Q3: 97%-100%) sessions. Moderate-to-vigorous PA and walking capacity increased after the programme without significant effect on body composition. Conclusion: Supervised home-based exercise sessions are an effective strategy to improve PA in women with PWS who are less active than women matched for adiposity.