OBJECTIVES: High-dose vitamin supplementation (HDVS)has recently been demonstrated to be of benefit for the prevention of progression of age-related macular degeneration (AMD) by the investigators of the Age-Related Eye Disease Study (AREDS), a National Eye Institute-sponsored randomized clinical trial. The aim of our study was to determine the cost-utility of HDVS in patients with the moderately advanced form of "dry" AMD. The analysis was performed from the perspective of a third party-insurer who was considering adding HDVS to their list of insured benefits. METHODS: Various decision analyses, based on Markov processing, were performed. Our models incorporated published data from the AREDS, our own patient-based utilities (n=127) and anticipated reductions in the need for treatments and services needed to treat the "wet" form of this disease. In addition, we created a cost-utility model by considering incremental medical costs incurred through the use of HDVS. Various sensitivity analyses were carried out to determine the robustness of our models. RESULTS: Our decision analysis, based on patient-derived utilities, demonstrated that HDVS with both antioxidants and zinc was found to be the preferred method of action, as it was associated with an expected relative gain in utility of 2.9 percent. Monte Carlo simulation demonstrated that the observed difference between treatment and placebo was statistically significant (p=0.021). Our cost-effective model, which employed a 5% discount rate, demonstrated that the cost per quality-of-life adjusted year (QALY) associated with high dose vitamin supplementation, when applied to patients with the moderately advanced form of dry age-related macular degeneration (group 3 or 4 disease according to the AREDS), was $2816.63. CONCLUSION: High-dose vitamin supplementation of patients with the moderately advanced form of "dry" age-related macular degeneration can be considered to be a very cost-effective strategy when used to prevent progression of AMD.