Several recent studies have focused on the association between the promoter polymorphisms 786T/C of the endothelial nitric oxide synthase (eNOS) gene and susceptibility to atrial fibrillation (AF); however, results have been conflicting. We searched Medline, Embase, and the ISI Web of Science through July 1, 2011. Five studies with 1,130 AF cases and 2,340 controls were selected. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated based on fixed- and random-effects models. There was no overall association between eNOS 786T/C and AF risk. In subgroup analysis, stratified by ethnicity, we observed a positive association between the eNOS 786T/C polymorphism and AF risk among Caucasians but not among mixed populations. When stratifying by control source, the overall ORs for population- and hospital-based studies were 1.07 (95% CI, 0.50-2.30) and 0.79 (95% CI, 0.65-0.97) for CC vs. 22T carriers, respectively. In the studies with a sample size greater than 200, the eNOS 786T/C polymorphism decreased AF risk (OR [95% CI]: 0.79 [0.64-0.97] for CC vs. T carriers). This meta-analysis suggests that the 786T/C polymorphism of the eNOS gene is protective against AF risk among Caucasians. Additional large studies based on diverse populations are required to validate this conclusion.