Tramadol is a central analgesic that seems to have fewer side effects and a lower abuse potential than classical opioids. Since the treatment of restless legs syndrome (RLS) with levodopa or classical opioids is problematic, new treatment possibilities would be valuable. We treated 12 patients who fulfilled at least the minimal diagnostic criteria proposed by the International Restless Legs Syndrome Study Group as well as the criteria proposed by Gibb and Lees, some of them treatment resistant or prone to side effects of previous medications, with 50 to 150 mg of tramadol per day in an open study. The follow-up lasted from 15 to 24 months. Ten patients reported clear amelioration and 1 reported slight amelioration of their symptoms, while 1 reported no effect. Tramadol was described to be the most effective treatment and free of side effects when compared with several other treatments. No major tolerance against treatment effect emerged among those who needed only a single evening dose. Compared with other treatments for RLS, tramadol seems to be superior in some cases, possibly because of its unique pharmacodynamic profile. Controlled studies are needed. Meanwhile, we believe that tramadol should be considered before other opioids are prescribed. We recommend intermittent treatment and careful monitoring.