Abstract Objective Since limited data exist on adults with Prader–Willi syndrome (PWS) and growth hormone (GH) treatment, we report our experience on the effects of treatment for one year on body composition, physical activity, strength and energy expenditure, diet, general chemistry and endocrine data with quality of life measures. Design We studied 11 adults with PWS (6F:5M; average age = 32 yrs) over a 2 year period with GH treatment during the first year only. Electrolytes, IGF-I, glucose, thyroid, insulin, lipids, body composition, physical activity and strength, diet, energy expenditure and quality of life data were collected and analyzed statistically using linear modeling at baseline, at 12 months following GH therapy and at 24 months after treatment cessation for 12 months. Results Total lean muscle mass was significantly increased (p < 0.05) during GH treatment along with moderate-vigorous physical activity and plasma IGF-I and HDL levels, but returned to near baseline after treatment. Percent body fat decreased during the 12 months of GH treatment but increased after treatment. Conclusions Previously reported beneficial effects of GH treatment in children with PWS were found in our adults regarding body composition, physical activity and plasma HDL and IGF-I levels. Several beneficial effects diminished to near baseline after cessation of GH treatment for 12 months supporting the continuation of treatment in PWS into adulthood and possibly adults not previously treated during childhood.