Abstract Introduction Erectile dysfunction (ED) has a significant negative impact on the quality of life of patients, while also presenting challenges due to the limited access to effective treatment options. Given ED is recognized as a precursor for other chronic health conditions, increasing patient access to ED treatment through men’s health programs may provide economic benefits to a healthcare system through revenue generated from subsequent patient care for other comorbidities. Objective This study quantified the incremental downstream revenue generated from treating men with ED with an inflatable penile prosthesis (IPP) compared to men without ED. Methods This retrospective study used the 100% Medicare Standard Analytical Files to identify men aged 65 years or older with ED who underwent IPP implantation (Current Procedural Terminology 54405) in a hospital outpatient setting between January 1, 2016 and December 31, 2021. To capture 5-year downstream revenue, patients were required to have continuous Medicare Parts A and B enrollment for 12 months pre-index IPP and five years post-index IPP discharge date. Propensity score matching (PSM) was used to match men with ED who received an IPP to men without ED based on demographic and clinical characteristics. Revenue was defined as the sum of the payment for patient services received by hospitals from Medicare, other payor paid amounts, and patient deductibles, copayment, and coinsurance. The total revenue generated was estimated as follows: 1-year pre-IPP, 1-year post-IPP, and 5-year cumulative post-IPP. The 1-year and 5-year downstream revenue was captured post-IPP discharge date and excluded the revenue generated from the index IPP encounter. Revenue was inflated to 2022 US dollars. The mean values and their corresponding standard deviations (SD) were reported. Results Before PSM, the study identified 3,367 men with ED who received IPP and 10,609 men without ED or IPP (mean age: 70; White: 77% vs 79%; Southern region: 53% vs 45%; and Elixhauser comorbidity index score ≥3: 21% vs 20%). Among men undergoing IPP, the average revenue generated was $6,152 (SD: $12,934) at 1-year pre-IPP and $7,898 (SD: $17,794) at 1-year post-IPP. After PSM, the men with ED who received IPP showed a significantly higher 5-year cumulative revenue (n=2,905; mean=$34,571 [SD=$50,234]) compared to the men without ED (n=7,462; mean=$3,189 [SD=$11,527]), respectively. The 5-year cumulative average revenue varied by type of diagnosis: circulatory disease (n=1,597; cost difference=$10,258), urology (n=1,358; cost difference=$2,013), diabetes diagnosis (n=562; cost difference=$2,646), and prostate cancer diagnosis (n=551; cost difference=-$1,043). All statistical analysis results post-PSM are significant at p-value less than 0.05. Conclusions Men with ED who received IPP generated substantially higher revenue for the healthcare system over a 5-year period, nearly ten times as much, compared to men without ED, excluding the initial cost of the IPP procedure. These findings emphasize the financial implications of implementing an advanced ED program aimed at improving access to necessary care for these patients. Healthcare facilities can leverage these insights to effectively allocate resources to deliver critical healthcare to men with ED. Disclosure Yes, this is sponsored by industry/sponsor: Boston Scientific. Clarification: Industry initiated, executed and funded study. Any of the authors act as a consultant, employee or shareholder of an industry for: This study was funded by Boston Scientific. Abimbola O. Williams, Sirikan Rojanasarot, Gregory Moore, Alysha M. McGovern, Liesl M. Hargens, and Erin Turner are employees of Boston Scientific. Paurush Babbar is a practicing urologist at The Urology Group in Cincinnati, Ohio and discloses no financial interests. Andrew Sun is a practicing urologist at Urology Partners of North Texas and serves as a consultant for Boston Scientific, Endo Pharmaceuticals, and Marius Pharmaceuticals. Paurush Babbar and Andrew Sun were not compensated for their participation in this study.