Aim: We have previously shown that 1 year of growth hormone (GH) treatment to adults with Prader-Willi syndrome (PWS) has beneficial effects on body composition. The aim of the present observational study was to re-evaluate our cohort, with focus on long-term GH treatment. Methods: Seven men and seven women, median age 31 years, were available for follow-up for 6 years. Nine were on GH treatment for 5 years. Body composition was measured with Dual Energy X-ray absorptiometry (DXA). Results: In six GH treated patients with genetically verified PWS there was a substantial increase in lean body mass of 5 kg (p = 0.031) and a concomitant, however, non-significant, decrease in body fat of 5% (p = 0.156). The changes in the genetically verified patients without GH treatment were small and unsystematic. No compliance problems were reported. Only one non-GH-treated woman developed overt diabetes. Conclusion: Despite inherent behavioural problems it was possible to continue GH injections for 5 years with sustained favourable effects on body composition without clinically, significant side effects.