Abstract Disclosure: M. Amiri: None. S. Hatoum: None. D. Hopkins: None. R.P. Buyalos: Employee; Self; Fertility & Surgical Associates of California. U. Ezeh: Stock Owner; Self; Concentric Analgesics, Inc. L.A. Pace: None. F. Bril: None. R. Azziz: Advisory Board Member; Self; Arora Forge. Consulting Fee; Self; Rani Therapeutics, Fortress Biotech, Spruce Biosciences, Core Access Surgical Technolgies. Grant Recipient; Self; Foundation for Research and Education Excellence, Ferring Pharmaceuticals. Stock Owner; Self; Martin Imaging. Background: PCOS is a complex genetic trait and the most common endocrine disorder of women, with significant cardio-metabolic and reproductive morbidities. PCOS is clinically evident in 5%-15% of all reproductive-aged women globally. It has been hypothesized that the global obesity epidemic is driving the high prevalence of PCOS. Objective: To determine the extent that obesity contributes to the development of PCOS globally. Materials and methods: PubMed and Embase databases were systematically searched to identify studies published through December 2022 recording the prevalence of PCOS in unselected populations globally. We then compared the PCOS prevalence with the prevalence of obesity in the population, i.e., country-based, using WHO data, with one exception. Linear regression was used to evaluate these associations, based on each of the three diagnostic criteria used by the studies (1990 NIH, 2003 Rotterdam, 2006 AE-PCOS). The grade of the studies was also assessed according to recruitment design: grade 1 (community-based), grade 2 (unselected subjects undergoing an evaluation for non-medical reasons), and grade 3 (subjects recruited through advertisement or if recruitment approach was not clear). Results: Of 6211 studies retrieved from databases and other resources, a total of 54 studies including 78,592 women of reproductive age were included in this systematic review. Forty-seven studies identified PCOS based on direct assessment, while 7 relied solely on self-assessment methods using questionnaires without comprehensive physical or hormonal evaluations. The studies were distributed by recruitment grade, including 20 grade 1, 17 grade 2, and 17 grade 3 studies. The average estimated prevalences of PCOS were 8.52%, 11.84%, and 12.78%, according to 1990 NIH, 2003 Rotterdam, and 2006 AE-PCOS, respectively. The % obesity in the populations studied varied widely, from 0.7% to 44.6%. Linear regression revealed no significant associations between the obesity prevalence in a population and its PCOS prevalence based on the diagnostic criteria of NIH (r= -0.01, P= 920), Rotterdam (r= 0.08, p= 0.476), and AE-PCOS (r= -0.07, p= 0.723) criteria when all studies, regardless of recruitment design, were considered. Similarly, when considering only studies of higher recruitment quality (namely 1 and 2), no significant relationship between obesity prevalence and PCOS prevalence based on the NIH (r= -0.09, p= 0.723), Rotterdam (r= 0.05, p= 0.702) and AE-PCOS (r= - 0.05, p= 0.822) criteria was detected. Conclusion: Our study results indicate no association between the prevalence of PCOS and that of obesity globally, in populations with a wide variation in the prevalence of obesity. These data indicate that obesity plays a limited role in the development of PCOS, although it likely worsens the metabolic phenotype. Funding: Foundation for Research and Education Excellence. Presentation Date: Saturday, June 17, 2023