Background and aims: Although many observational studies have suggested that alcohol intake was associated with incident atrial fibrillation (AF), controversy remains. This study aimed to examine the causal association of alcohol intake with the risk of AF. Methods and results: Two-sample Mendelian randomization (MR) analysis was performed to estimate the causal effects of alcohol consumption, alcohol dependence, or alcohol use disorder identification test (AUDIT) scores on AF. Summary data on single nucleotide polymorphisms (SNPs) associated with AF were obtained from a genome-wide association study (GWAS) with up to 1,030,836 participants. The fixedand random-effect inverse-variance weighted (IVW) methods were used to calculate the overall causal effects. MR analysis revealed nonsignificant association of genetically predicted alcohol consumption with risk of AF using fixedand random-effect IVW approaches (odds ratio (OR) [95% confidence interval (CI)] = 1.004 [0.796-1.266], P = 0.975; OR [95% CI] = 1.004 [0.766-1.315], P = 0.979). Genetically predicted alcohol dependence was also not causally associated with AF in the fixedand random-effect IVW analyses (OR [95% CI] = 1.012 [0.978-1.048], P = 0.490; OR [95% CI] = 1.012 [0.991-1. 034], P = 0.260). There was no significantly causal association between AUDIT and AF in the fixed and random-effect IVW analyses (OR [95% CI] = 0.889 [0.433-1.822], P = 0.748; OR [95% CI] = 0.889 [0.309-2.555], P = 0.827). Sensitivity analyses indicated no evidence of pleiotropy and heterogeneity in statistical models. Conclusions: This MR study did not find evidence of a causal association between alcohol intake and AF. (C) 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.