PurposeTo assess the effect of tadalafil use on progression of early/intermediate to advanced exudative or non-exudative age-related macular degeneration (AMD) in a real-world population. DesignRetrospective cohort study utilizing Optum's de-identified Clinformatics® Data Mart Database (CDM). MethodsPatients were included from January 2015 to December 2020 aged 55 and older with an index International Classification of Diseases, Tenth Revision (ICD-10) diagnosis of early or intermediate AMD who had a 2-year period of continuous enrollment prior to the index diagnosis date (lookback period), 5 years of continuous follow-up, and who did not meet any exclusion criteria (claims for a phosphodiesterase-5 (PDE-5) inhibitor other than tadalafil during the study, diagnosis of advanced non-exudative or exudative AMD, or claims for wet AMD treatment during the lookback period). Treated patients with claims for tadalafil during the study period were matched 1:1 to untreated controls by age, sex, race, and smoking status. We assessed the effect of any tadalafil use, high (≥2700 mg) cumulative dose tadalafil vs. matched untreated controls, high (>2700 mg) vs. low (<2700 mg) cumulative dose tadalafil, and the 2-year cumulative dose of tadalafil (per 100 mg) as a continuous variable on incidence of progression to advanced exudative or non-exudative AMD during the 2-year follow-up. ResultsThere was no significant difference in odds of progression to exudative AMD or advanced non-exudative AMD in the control vs treated groups (OR=0.802, 95% CI (0.558-1.152), p=0.233; OR=1.326, 95% CI (0.757-2.323), p=0.323). High (≥2700 mg) cumulative dose tadalafil was not associated with a significant difference in odds of progression to exudative AMD or advanced non-exudative AMD when compared to the matched controls (OR=0.455, 95% CI (0.202-1.025), p=0.057; OR=1.000, 95% CI (0.318-3.142), p=1.000). There was no significant difference in odds of progression to exudative AMD or advanced non-exudative AMD in the high (>2700 mg) vs. low (≤2700 mg) cumulative dose tadalafil (OR=590, 95% CI (0.296-1.177), p=0.134; OR=1.039, 95% CI (0.440-2.460), p=0.931). Lastly, there was no significant difference in odds of progression to exudative AMD or advanced non-exudative AMD when assessing the 2-year cumulative tadalafil dose (per 100 mg) as a continuous variable (OR=1.000, 95% CI (1.000-1.000), p=0.305; OR=1.000, 95% CI (1.000-1.000), p=0.878). ConclusionIn a retrospective cohort study of a large nationwide health insurance claims database, tadalafil use was not associated with progression of AMD.