BACKGROUND: Restless legs syndrome is very common in hemodialysis patients however there are no comparative studies assessing the effectiveness of a non-pharmacological treatment to a classical treatment on parameters related to syndromes' severity and quality of life. METHODS: In this randomized, partially double blind, placebo controlled trial, thirty two hemodialysis patients with restless legs syndrome were randomly assigned into three groups: (1) the exercise training group (n = 16), (2) the dopamine agonists group (ropinirole 0.25 mg/d) (n = 8) and (3) the placebo group (n = 8). The intervention programs lasted 6 months. Restless legs syndrome severity was assessed using the international severity scale, physical performance by a battery of tests, muscle size and composition by computed tomography, body composition by dual energy x-ray absorptiometry, while depression score, sleep quality, daily sleepiness and quality of life were assessed through questionnaires. RESULTS: Exercise training and dopamine agonists were effective in reducing syndrome's symptoms by 46% (p = 0.009) and 54% (p = 0.001) respectively. Within group changes revealed that both approaches significantly improved quality of life (p < 0.05), however, only the dopamine agonists significantly improved sleep quality (p = 0.009). Within group changes showed a tendency for lean body mass improvements with dopamine agonists, this reached statistical significance only with the exercise training (p = 0.014), which also reduced fat infiltration in muscles (p = 0.044) and improved physical performance (p > 0.05) in various tests. Between group changes detect significant improvements with both exercise and dopamine agonists in depression score (p = 0.003), while only the dopamine agonist treatment was able to significantly improve sleep quality, compared to exercise and placebo (p = 0.016). CONCLUSIONS: A 6-month exercise training regime was as effective as a 6-month low dosage dopamine agonist treatment in reducing restless legs syndrome symptoms and improving depression score in uremic patients. Further research is needed in order to show whether a combination treatment could be more beneficial for the amelioration of RLS. TRIAL REGISTRATION: NCT00942253.

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