The aim of this study was to test the hypothesis that ongoing aspirin therapy preserves neutrophil apoptosis after cardiac surgery with cardiopulmonary bypass (CPB) by a cyclooxygenase mechanism. Twenty patients undergoing coronary revascularization with CPB were enrolled in a prospective cohort study. Patients who had continued taking 300 mg of aspirin until the day before surgery (n = 10) were compared with 10 patients not taking aspirin or who had discontinued it more than 5 days before surgery. Neutrophils were isolated from arterial blood before and 6 h after surgery and apoptosis was measured after 24 h in culture using flow cytometry. Serum was collected and assessed for IL-6, IL-8 and PGE2 by enzyme-linked immunoabsorbant assay. Patients were followed for clinical indices of sepsis for 7 days postoperatively. Spontaneous rates of neutrophil apoptosis were significantly reduced in postoperative compared with preoperative samples. There was no difference between aspirin and control preoperative neutrophil apoptosis rates (23.0% ± 11.3% vs. 23.0% ± 20.7%, P = 0.99). Postoperative neutrophil apoptosis was delayed in control patients (3.6% ± 1.2% apoptosis), but this was significantly (P = 0.045) reversed in the aspirin-treated group (7.2% ± 5.1% apoptosis). There were lower postoperative PGE2 levels in the aspirin group (136 ± 69 pg/mL vs. 372 ± 210 pg/mL, P = 0.04). There was no difference in clinical indices of sepsis. We conclude that the delay in postoperative neutrophil apoptosis is significantly preserved in patients taking 300 mg of aspirin on the day before surgery. This was associated with greater inhibition of PGE2, consistent with the hypothesis that aspirin exerts its effect on apoptosis after CPB via a cyclooxygenase-mediated mechanism.