On-pump cardiac surgery may trigger inflammation and accelerate platelet cyclooxygenase-1 renewal, thereby modifying low-dose aspirin pharmacodynamics. Thirty-seven patients on standard aspirin 100mg once-daily were studied before surgery and randomized within 36 hours post-surgery to 100mg once-daily, 100mg twice-daily or 200mg once-daily for 90 days. On day 7 post-surgery, immature and mature platelets, platelet mass, thrombopoieitin, glycocalicin, leukocytes, C-reactive protein, and interleukin-6 significantly increased. Interleukin-6 significantly correlated with immature platelets. At day 7, patients randomized to 100mg once-daily showed a significant increase in serum thromboxane (TX)B2 within the 24-hour dosing interval and urinary TXA2 metabolite (TXM) excretion. Aspirin 100mg twice-daily lowered serum TXB2 and prevented post-surgery TXM increase (p<0.01), without affecting prostacyclin metabolite excretion. Following cardiac surgery, shortening the dosing interval, but not doubling the once-daily dose, rescues the impaired antiplatelet effect of low-dose aspirin and prevents platelet activation associated with acute inflammation and enhanced platelet turnover. This article is protected by copyright. All rights reserved.