OBJECTIVES: Positive return on investment (ROI) for disease management (DM) programs has generally been limited to those managing congestive heart failure or multiple disease conditions. It is the objective of this model to evaluate the ROI of a glaucoma-screening DM program in Commercial vs. Senior member populations. METHODS: An interactive Excel-based 14-year economic model previously developed to assess the payer costs associated with screening and early treatment of glaucoma patients vs. non-screening of asymptomatic progressive disease was extended to dynamically model the drug treatment component. Treatment costs and disease progression rates were taken from the published literature. Drug costs were based on average wholesale price cost with consideration of contractual discounts and patient co-payment. The primary economic endpoint was the ratio of reduced annual treatment costs compared to annual program costs. Multi-factor sensitivity analyses were conducted. RESULTS: In a Commercial population, total annual costs to “screen and treat” vs. a strategy of no screening was estimated to be $0.62 PMPM vs. $0.80 PMPM respectively (a difference of $0.12 PMPM in favor of screening). In the Senior population, these costs were estimated to be $6.66 PMPM vs. $7.94 PMPM respectively (a difference of $1.28 PMPM in favor of screening). With estimated program costs of $0.009 PMPM and $0.167 PMPM in the Commercial vs. Senior populations respectively, the calculated potential ROI was estimated to be 2.6 and 1.7 respectively for these programs. CONCLUSION: The early identification and treatment of glaucoma in accordance with established evidence-based clinical practice guidelines represents a more cost-effective strategy as compared to non-screening of at risk populations. Total annual costs for a glaucoma-screening disease management program are estimated to demonstrate a positive ROI in both Commercial and Senior populations. These findings may help promote the interest of payers in implementing pertinent quality improvement and HEDIS-related efforts.