Atrial fibrillation (AF) is a major risk factor for stroke. Although acute alcohol intake has been associated with AF, it is not known whether long-term alcohol consumption in moderation is associated with an increased risk of AF. We used a risk set method to assess the relation of long-term alcohol consumption to the risk of AF among participants in the Framingham Study. For each case, up to 5 controls were selected and matched for age, age at baseline examination, sex, cohort, baseline history of hypertension, congestive heart failure, and myocardial infarction. Within each risk set, alcohol consumption was averaged from baseline until the examination preceding the index case of AF. Of the 1,055 cases of AF occurring during a follow-up of >50 years, 544 were men and 511 were women. In a conditional logistic regression with additional adjustment for systolic blood pressure, age at baseline examination, education, and cumulative history of myocardial infarction, congestive heart failure, diabetes mellitus, left ventricular hypertrophy, and valvular heart disease, the relative risks were 1.0 (reference), 0.97 (95% confidence interval [CI] 0.78 to 1.22), 1.06 (95% CI 0.80 to 1.38), 1.12 (95% CI 0.80 to 1.55), and 1.34 (95% CI 1.01 to 1.78) for alcohol categories of 0, 0.1 to 12, 12.1 to 24, 24.1 to 36, and >36 g/day, respectively. In conclusion, our data indicate little association between long-term moderate alcohol consumption and the risk of AF, but a significantly increased risk of AF among subjects consuming >36 g/day (approximatively >3 drinks/day).