Fibromyalgia syndrome (FMS) frequently presents with autonomic and/or functional symptoms. Tropisetron, a selective serotonin-3 antagonist, is widely used for the treatment of this disease. However, its effects on autonomic function are not well known. In the present study, we evaluated whether tropisetron improved cardiac autonomic symptoms in FMS. Thirty-six patients were treated with physiotherapy and 5 mg tropisetron intravenously for 5 days. An additional 36 patients were treated with physiotherapy alone. Thirty-six volunteers served as healthy controls. The ISAX apparatus was used for spectral analyses of cardiac R-R intervals. High frequencies and mid frequencies were analysed to assess sympathetic and parasympathetic activity. The findings were correlated with pain intensity. ISAX findings were significantly different in FMS patients compared to healthy controls and did not correlate with pain perception. Ten of 12 pathological parameters disappeared during treatment in the tropisetron group. Our results indicate that tropisetron reduced not only pain perception but also had a favourable effect on cardiac dysfunction during treatment.