To comprehensively review and evaluate the direct costs of endometriosis.We systematically reviewed studies published since 1990, and conducted an analysis of publicly available national databases (Healthcare Cost and Utilization Project and National Ambulatory Medical Care Survey/National Hospital Ambulatory Medical Care Survey) in the United States. We assessed: [1] the overall economic impact of endometriosis; [2] the direct costs associated with specific treatments; and [3] the indirect costs of endometriosis associated with reduced work productivity.Of 13 published studies meeting inclusion criteria, 11 (85%) addressed direct costs, a few studies addressed outpatient costs or indirect costs, and no study quantified the economic impact among adolescents. Direct endometriosis-related costs were considerable and appeared driven by hospitalizations. Our database analysis found: [1] as endometriosis-related hospital length of stay steadily declined from 1993 to 2002, per-patient cost increased 61%; [2] adolescents (aged 10-17 years) had endometriosis-related hospitalizations; [3] approximately 50% of >600,000 endometriosis-related ambulatory patient visits involved specialist care; and [4] females 23 years old or younger constituted >20% of endometriosis-related outpatient visits.Health economic information for endometriosis is scarce, limiting our understanding of its overall economic impact. Nevertheless, the literature and other available data suggest that endometriosis places a considerable burden on patients and society.