PURPOSE: Vascular risk factors, including alcohol intake, have been hypothesized to play a role in the development of age-related macular degeneration (AMD). We examined the relationship of alcohol intake with AMD in the Physicians' Health Study (PHS). METHODS: The PHS was a randomized trial of aspirin and beta-carotene among 22,071 U.S. male physicians age 40 to 84 years at entry. A total of 21,041 physicians with complete data on alcohol consumption and no AMD at baseline were included in this analysis. Proportional hazards models were used to estimate relative risks (RR) and 95% confidence interval (CI). RESULTS: During an average follow-up period of 12.5 years, 278 physicians were confirmed by medical record review to have incident AMD resulting in vision loss (acuity 20/30 or worse). After adjusting for age, randomized treatment assignment, and other potential risk factors, the RR for greater than or equal to 1 drink/week versus < 1 drink/week was 0.97 (CI: 0.78-1.21). For categories of alcohol intake, the RRs for those reporting alcohol consumption of < 1 drink/week, 1 drink/week, 2-4 drinks/week, 5-6 drinks/week, and greater than or equal to 1 drink/day were 1.00 (referent), 1.00 (0.65-1.55), 0.68 (0.44-1.04), 1.32 (0.89-1.95), and 1.27 (0.93-1.73), respectively. CONCLUSIONS: These prospective data indicate that alcohol intake is not appreciably associated with the risk of incident AMD. However, the width of the confidence intervals are compatible with a possible small effect (reduction or increase) in risk for low to moderate levels of alcohol intake, which warrant further investigation. Ann Epidemiol 1999;9:172-177. (C) 1999 Elsevier Science Inc. All rights reserved.