We aimed to determine whether polymorphisms in chromosome 4q25 are associated with postoperative atrial fibrillation (AF), long-term AF, postoperative or long-term stroke, and long-term survival after coronary artery bypass grafting. We performed genotyping for rs2200733 and rs10033464 in white participants (n = 1,166) from the TexGen genetic registry. The development of postoperative or long-term AF, postoperative or long-term stroke, and long-term mortality were ascertained. Both rs2200733 and rs10033464 were associated with postoperative AF (odds ratio [OR] 1.41, 95% confidence interval [CI] 1.04 to 1.91, and OR 1.47, 95% CI 1.05 to 2.06, respectively). Carriers of the risk allele (T) had an increased risk of postoperative AF with preoperative β blocker (BB) (for rs2200733, OR 1.47, 95% CI 1.004 to 2.16 for those taking a BB, and OR 1.13, 95% CI 0.73 to 1.73 for those not taking a BB; for rs10033464, OR 1.89, 95% CI 1.22 to 2.93 for those taking preoperative a BB, and OR 1.04, 95% CI 0.65 to 1.65 for those not taking a BB). Both rs2200733 and rs10033464 were also associated with long-term AF (hazard ratio 1.32, 95% CI 1.05 to 1.67, and hazard ratio 1.28, 95% CI 1.00 to 1.66, respectively). Carriers of rs2200733 had increased long-term mortality (hazard ratio 1.57, 95% CI 1.10 to 2.24). These variants were not associated with postoperative or long-term stroke. In conclusion, variants in 4q25 are associated with an increased risk of postoperative or long-term AF and, possibly, mortality in whites undergoing coronary artery bypass grafting, and could potentially affect the choice of therapy used to decrease postoperative AF.