Objectives: To determine the association between genetic variants on chromosome 4q25 and atrial fibrillation (AF) in a Taiwanese population. Methods: We enrolled 200 patients with AF (mean age: 67 ± 13 years) and 158 controls (mean age: 63 ± 10 years). The genotypes of five SNPs, RS2634073, RS2200733, RS13143308, RS2220427 and RS10033464, were determined using multiplex single base extension methods. Results: The distribution of the RS2200733 and RS10033464 genotypes did not significantly deviate from the Hardy-Weinberg equilibrium in the control group. The distribution of the RS2200733 genotypes differed significantly between the AF group and the controls (p = 0.03), whereas the distribution of the RS10033464 genotypes did not (p = 0.49). At RS2200733, patients with the CC genotype exhibited a 0.45 times higher risk of developing AF than those with the TT genotype (p = 0.02) and a recessive model was suggested (p = 0.01). After adjusting for various covariates, patients with the CC genotype remained recessively associated with a lower risk of developing AF than those with the TT genotype (odds ratio: 0.27, 95% confidence interval: 0.11–0.65; p < 0.01). Conclusions: In the Taiwanese, there is an association between SNP RS2200733 – but not RS10033464 – and the development of AF. Based on a recessive model of inheritance, individuals with SNP RS2200733 genotype CC are at a lesser risk of developing AF.