BACKGROUND: Several randomized clinical trials evaluated whether preoperative supplementation of omega-3 (n-3) polyunsaturated fatty acids protects against postoperative atrial fibrillation after cardiac surgery, a condition associated with increased cardiac and cerebral mortality. However, their efficacy remains still controversial. An updated meta-analysis was performed to clarify if preoperative n-3 polyunsaturated fatty acid supplementation prevents postoperative atrial fibrillation in patients undergoing cardiac surgery. METHODS: Articles were retrieved until November 2012 by screening electronic databases (PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials) and cross references. Two of us independently reviewed articles and agreed to select 8 randomized clinical trials. For each study, the incidence of atrial fibrillation in both the intervention and placebo groups was extracted to calculate odd ratio and 95% confidence intervals (CIs). Weighted study-specific estimates were combined using fixed (Mantel-Haenszel method) and random-effects (DerSimonian-Laird method) models. RESULTS: This meta-analysis includes 2687 patients (1337 in the intervention group) who underwent cardiac surgery. Pooled analysis using fixed-effects models showed a significant reduction (average, 16%; 95% CI, 1%-29%) in postoperative atrial fibrillation by preoperative n-3 polyunsaturated fatty acids. There was a low heterogeneity among studies (P = .07 and I(2) = 46%). By using a random-effects model, the reduction averaged 25% (odds ratio, 0.75; 95% CI, 0.57-1.00; P = .05). When isolated coronary artery bypass graft surgery was only considered (7 studies), a significant protection averaging 34% was observed in a fixed model (odds ratio, 0.66; 95% CI, 0.50-0.87; P = .003; I(2) = 26%, P = .23). CONCLUSIONS: A preoperative supplementation of n-3 polyunsaturated fatty acids significantly prevents the occurrence of postoperative atrial fibrillation in patients undergoing cardiac surgery, in particular coronary artery bypass surgery.