OBJECTIVES: The aim of this study is, first, to provide a systematic review of the international literature exploring endometriosis costs and, second, to calculate endometriosis costs in the US population. The review determines the level and drivers of endometriosis costs; appraises the methodological quality of cost studies; and proposes directions for designing future studies of endometriosis costs. METHODS: Information about endometriosis costs was derived from cost-of-illness analyses and cost analyses. A data extraction form and quality appraisal form was completed for each study. The calculation of endometriosis costs in the US population was based on estimates of (in)direct costs and endometriosis prevalence as derived from published sources. All costs were expressed in 2002 US dollars. RESULTS: The review indicated that annual healthcare costs and costs of productivity loss associated with endometriosis have been estimated at $2,801 and $1,023 per patient, respectively. Extrapolating these findings to the US population, this study calculated that annual costs of endometriosis attained $22 billion in 2002 assuming a 10% prevalence rate among women of reproductive age. To date, it is not possible to determine whether a medical approach is less expensive than a surgical approach to treating endometriosis in patients presenting with chronic pelvic pain. Evidence of endometriosis costs in infertile patients is largely lacking. Cost estimates were biased due to the absence of a control group of patients without endometriosis, inadequate consideration of endometriosis recurrence, and restricted scope of costs. There is a need for more and better-designed studies that carry out longitudinal analyses of patients until the cessation of their symptoms or that model the chronic nature of endometriosis. CONCLUSION: Our estimated costs of endometriosis in the US population are considerable, underlining the need for further research into cost-effective approaches to diagnosing and treating endometriosis.