OBJECTIVES: Endometriosis (the presence of endometrial-like tissue outside the uterus) affects 10% of women of reproductive age and is associated with dysmenorrhoea, pain at ovulation, dyspareunia, abnormal bleeding, chronic pelvic pain, fatigue, and infertility. This study aimed to calculate costs and health-related quality of life of women with endometriosis-associated symptoms treated in referral centres. METHODS: A prospective, international, multi-centre questionnaire-based survey measured costs and health-related quality of life in ambulatory care and in 12 tertiary care centres in ten countries. The study enrolled women with a diagnosis of endometriosis and with at least one centre-specific contact related to endometriosis-associated symptoms in 2008. The main outcome measures included health care costs, costs of productivity loss, total costs and quality-adjusted life years. Predictors of costs were identified using regression analysis. RESULTS: Data analysis of 909 women (63% response rate) demonstrated that the average annual total cost per woman was €9,579 (95% CI €8,559-€10,599). Costs of productivity loss of €6298 per woman were double the health care costs (€3113 per woman). Health care costs were mainly due to surgery (29%), monitoring tests (19%) and hospitalization (18%). The cost of medication accounted for 10% of health care costs.  At a prevalence rate of 7%, the annual burden of endometriosis-associated symptoms ranged from €0.8 billion in Denmark to €50 billion in the United States. Endometriosis-associated symptoms generated 0.809 quality-adjusted life years per woman. Decreased quality of life was the most important predictor of direct health care and total costs.  Costs were greater with increasing severity of endometriosis, presence of pelvic pain, presence of infertility, and higher number of years since diagnosis. CONCLUSIONS: The economic burden associated with endometriosis is high and is similar to other chronic diseases (diabetes, Crohn’s disease, rheumatoid arthritis). It arises predominantly from productivity loss, and is predicted by decreased quality of life.