OBJECTIVE To examine the effect of a long-term nutritional supplementation on age-related macular degeneration progression. METHODS In this prospective, double-blind, placebo-controlled study, 80 patients with intermediate age-related macular degeneration were randomized (2:1) to receive 1 tablet/day of a nutritional supplement containing a mixture of carotenoids, vitamins and omega-3 fatty acids or placebo. Age-related macular degeneration progression assessed by digital fundus photography (primary outcome) and best-corrected visual acuity were evaluated. Differences between arms were tested using chi-square test or Fisher's exact test. RESULTS Seventy-four patients completed the follow-up at 24 months (48 in the treated arm and 26 in the placebo arm). An age-related macular degeneration progression was observed in the 2.1% of patients of the treated arm and in the 15.4% of patients in the placebo arm (p = 0.05, Fisher's exact test). Best-corrected visual acuity data alone were not statistically significant among groups. CONCLUSIONS A clinically meaningful stabilization of intermediate age-related macular degeneration over a period of 2 years may be obtained by treating patients with a mixture of carotenoids, vitamins and omega-3 fatty acids.