Context: The polycystic ovary syndrome (PCOS) is the most common endocrine abnormality of reproductive-aged women today, affecting approximately 6.6% of unselected reproductive-aged women (∼4 million women in the United States) (1990 National Institutes of Health criteria), and potentially represents a significant financial burden to our health care. Objective: The objective of the study was to define, using current definitions and prevalence or incidence data, the minimal economic burden that PCOS in reproductive-aged women represents for the United States. Design: The study design was a literature review. Setting: The study was conducted at a tertiary care center. Patients or Other Participants: There were no patients or other participants. Intervention(s): We performed a systematic review of the published medical literature to identify studies evaluating epidemiology of reproductive-age PCOS and its clinical consequences and costs. We tied general societal cost data for the different health consequences to reproductive-age PCOS costs, using prevalence data. Main Outcome Measure(s): The main measure in the study was total health care-related economic costs. Results: We estimated the mean annual cost of the initial evaluation to be $93 million (2.1% of total costs), that of hormonally treating menstrual dysfunction/abnormal uterine bleeding to be $1.35 billion (31.0% of total), that of providing infertility care to be $533 million (12.2% of total), that of PCOS-associated diabetes to be $1.77 billion (40.5% of total), and that of treating hirsutism to be $622 million (14.2% of total). Conclusions: The total cost of evaluating and providing care to reproductive-aged PCOS women in the United States is $4.36 billion. Because the cost of the diagnostic evaluation accounted for a relatively minor part of the total costs (approximately 2%), more widespread and liberal screening for the disorder appears be a cost-effective strategy, leading to earlier diagnosis and intervention and possibly the amelioration and prevention of serious sequelae. Copyright © 2005 by The Endocrine Society.