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Purpose: Cost-effectiveness analyses (CEAs) quantify and compare both costs and measures of efficacy for different interventions. As the costs of glaucoma management to patients, payers, and physicians are increasing, we seek to investigate the role of CEAs in the field of glaucoma and how such studies impact clinical management. Methods: We adhered to the “Preferred Reporting Items for Systematic Reviews and Meta-analyses” guidelines for our systematic review structure. Eligible studies included any full-text articles that investigated cost-effectiveness or cost-utility as it relates to the field of open angle glaucoma management in the United States. Risk of bias assessment was conducted using the validated Joanna Briggs Institute Critical Appraisal Checklist for Economic Evaluations. Results: Eighteen studies were included in the review. Dates of publication ranged from 1983 to 2021. Most of the studies were published in the 2000s and performed CEAs in the domains of treatment/therapy, screening, and adherence for patients with primary angle open glaucoma. Of the 18 articles included, 14 focused on treatment, 2 on screening, and 2 on adherence. Most of these studies focused on the cost-effectiveness of different topical medical therapies, whereas only a few studies explored laser procedures, surgical interventions, or minimally invasive procedures. Economic models using decision analysis incorporating state-transition Markov cycles or Montecarlo simulations were widely used, however, the methodology among studies was variable, with a wide spectrum of inputs, measures of outcomes, and time horizons used. Conclusion: Overall, we found that cost-effectiveness research in glaucoma in the United States remains relatively unstructured, resulting in unclear and conflicting implications for clinical management.