OBJECTIVE:To investigate the feasibility of progressive resistance training for people with Prader-Willi syndrome (PWS), who have muscle weakness and very low muscle mass. DESIGN:Randomised controlled trial with concealed allocation, assessor blinding and intention-to-treat analysis. SETTING:Community gymnasium. PARTICIPANTS:Sixteen participants with PWS (eight female; mean age 25 years) were randomly assigned with 1:1 allocation to an experimental (n=8) or control group (n=8). INTERVENTION:Progressive resistance training was performed twice a week for 10 weeks. The training was supervised one-to-one by a physiotherapist and comprised seven exercises. The control group continued their usual activities and were offered the training after follow-up assessment. MAIN OUTCOME MEASURES:Three domains of feasibility were evaluated: implementation (attendance and adherence), practicality (safety) and limited efficacy testing. Muscle strength (one repetition maximum for chest and leg press), physical function (box stacking test, timed stairs climb), muscle composition (US) and body composition (whole-body DXA scan) were measured before and after the intervention. RESULTS:Participants attended 92% of scheduled sessions and adhered by progressing their training resistance by 82% (range 60-140%). There was one unexpected serious adverse event unrelated to the intervention and several non-serious expected adverse events related to the intervention. Estimates of standardised mean differences indicated moderate to large effects in favour of the experimental group for arm (0.92, 95%CI -0.11 to 1.95) and leg strength (0.78, 95%CI -0.27 to 1.83). The effect was uncertain for secondary outcomes. CONCLUSIONS:There is preliminary evidence showing progressive resistance training is feasible for people with Prader-Willi syndrome and may increase muscle strength. Clinical Trial Registration Australia New Zealand Clinical Trials Registry ACTRN12616000107426.