The objective was to evaluate the effectiveness of a self-management patient education programme for fibromyalgia syndrome (FMS) as compared with usual care education in inpatient rehabilitation. In a multicentre cluster-randomized controlled trial, 583 inpatients in 3 rehabilitation centres received an advanced self-management patient education programme or usual care education. Patients completed questionnaires at admission, discharge and after 6 and 12 months. Primary outcomes were disease- and treatment-specific knowledge at discharge, and self-management-competencies after 6 months. Secondary outcomes included satisfaction, attitudes, coping competencies, psychological distress and health impairment. We found a medium-sized effect on disease- and treatment-specific knowledge at discharge (P < 0.05, Cohen's d = 0.45, 95% CI = 0.27-0.63), and small effects for subjective knowledge, pain-related control, self-monitoring and insight, communication about disease, action planning for physical activity and treatment satisfaction (all P < 0.05). Only the effect on knowledge persisted for 6 and 12 months. This advanced education programme seemed to be more effective in the short term than usual education. However, intermediate- and long-term effects did not emerge. While superior long-term effects on knowledge as well as short-term effects on self-management skills may suggest implementation, additional long-term effects on other patient-relevant outcomes would be desirable. Trial registration: German Clinical Trials Register, DRKS00008782, Registered 8 July 2015.