Purpose. To investigate the effect of N-acetylcysteine on preventing pump-induced oxidoinflammatory response during cardiopulmonary bypass (CPB). Methods. Forty patients undergoing coronary artery bypass grafting (CABG) were randomly divided into a study group (n = 20), given 50 mg kg-1 N-acetylcysteine intravenously for 3 days, and a control group (n = 20) given saline. Serum samples were collected for measurement of myeloperoxidase (MPO), malondialdehyde (MDA), interleukin-6, α1-acid glycoprotein (AAGP), and C-reactive protein (CRP) during surgery and postoperatively. Results. The MPO and MDA values showed a similar pattern during and after CPB in the study group, with significantly less variance than in the control group. Interleukin-6 showed similar patterns in the two groups, but the data from 30 min after the start of CPB and from 6 h post-CPB were significantly different. The AAGP and CRP values were both elevated during CPB in the two groups without a significant difference, but 6 and 24 h post-CPB, the values were significantly higher in the control group than in the study group. Conclusions. N-Acetylcysteine decreased pump-induced oxidoinflammatory response during CPB, suggesting that it could be a novel therapy for assisting in the prevention of CBP-induced oxidoinflammatory damage.