Objective: Cardiopulmonary bypass remains associated with significant morbidity and mortality, in part caused by a systemic inflammatory response that is unpredictable and variable among patients. Several limited studies have suggested associations of cytokine plasma levels or gene polymorphisms with outcome after cardiopulmonary bypass. The present study was to determine the relationships between several circulating cytokines and their polymorphisms (single nucleotide polymorphisms), and the occurrence of postoperative clinical events in patients who underwent coronary artery bypass grafting under cardiopulmonary bypass. Methods: Patients were genotyped for single nucleotide polymorphisms of LTA (Cys13Arg, +252A>G), TNF (-308G>A), IL6 (-597G>A, -572G>C, -174G>C), IL10 (-592C>A, c.117C>T), and APOE (Cys112Arg, Arg158Cys). Serum samples were collected preoperatively, immediately after cardiopulmonary bypass, and at different postoperative time points to measure cytokine serum levels by enzyme-linked immunosorbent assay. The clinical end point was the composite of postoperative death, low cardiac output syndrome, myocardial infarction, sepsis, and acute renal insufficiency. Results: Single nucleotide polymorphisms IL6-572GC+CC/IL10-592CC were associated with the clinical end point (P = .032 and P = .009, respectively). In addition to preoperative clinical conditions, the other factor associated with the clinical end point was interleukin-10 plasma levels 24 hours after surgery (P = .017). On the basis of these results, a predictive model of postoperative complications after coronary artery bypass grafting was created. Conclusions: Our data suggest that focused genetic testing of the IL6-572G>C and IL10-592C>A single nucleotide polymorphisms might be a tool for identifying patients at the highest risk of poor tolerance to the inflammatory response to cardiopulmonary bypass and for implementing strategies to mitigate it, provided the generalization of these tests makes them reasonably affordable and thus favorably shifts their cost-to-benefit ratio. © 2012 by The American Association for Thoracic Surgery.