Purpose: To evaluate the association between cholesterol-lowering medications and age-related macular degeneration (AMD). Design: Case-control study. Participants: The Atherosclerosis Risk in Communities study is a prospective, population-based, cohort study conducted in 4 communities across the United States. A total of 15792 individuals aged 45 to 65 years were enrolled between 1987 and 1989; fundus photographs were added to the study protocol at the 6-year follow-up (1993-1995). Cases were subjects who were identified as having AMD after applying a standard definition to their fundus photographs; controls did not have AMD. Methods: The use of cholesterol-lowering medications at any time during the study was determined and compared between cases and controls, adjusting for the potentially confounding effect of demographic, behavioral, and medical characteristics. Main Outcome Measures: Presence of AMD and the use of cholesterol-lowering medications. Results: A total of 871 AMD cases and 11 717 controls were identified. Of the AMD cases, 11% made use of cholesterol-lowering medications, as compared with 12.3% of controls (odds ratio [OR], 0.89; 95% confidence interval [CI], 0.71-1.11). Adjusting for the confounding influence of age, gender, and race revealed a statistically significant relationship between AMD and use of cholesterol-lowering medications (OR, 0.79; 95% CI, 0.63-0.99). Conclusions: The results of this study add to the growing body of evidence that cholesterol-lowering medications may reduce the risk of developing AMD. Additional research is needed to document the mechanism responsible for this association. A clinical trial of the impact of statins on AMD deserves consideration. © 2005 by the American Academy of Ophthalmology.