The objective was to investigate whether the platelet dysfunction in cardiac surgery is caused by hemodilution or by shear stress due to cardiopulmonary bypass (CPB). Platelet count and function were prospectively analyzed in two groups of patients undergoing cardiac surgery either with or without CPB (n = 40). In the first study (n = 20; 10 patients with and 10 without CPB), platelet counts were assessed at seven time points. In the second study (n = 20; 10 patients with and 10 without CPB), platelet function was studied with platelet aggregometry at different points during surgery: (a) after induction of anesthesia; (b) after sternotomy; and (c) 1 h after heparin. In the first study, the CPB group showed a significant decrease in platelet count starting after sternotomy (230 +/- 34 vs. 182 +/- 25, P < 0.05) and a maximum decrease at day 1 postoperative (96 +/- 34, P < 0.05). A similar observation was made in the non-CBP group. In the second study, a significant decrease of ADP (54 +/- 13% vs. 38 +/- 9%, P < 0.05), AA (76 +/- 16% vs. 22 +/- 14%, P < 0.05), and Collagen (66 +/- 13% vs. 37 +/- 11%, P < 0.05) induced platelet aggregation was observed at MOMENT d compared to the beginning of surgery in the CPB group. In the non-CBP group a significant decrease was observed in AA-induced platelet aggregation at MOMENT d (83% +/- 4 vs. 44% +/- 14, P < 0.05). The reduction in platelet count is similar with or without cardiopulmonary bypass and is due to pure hemodilution. Platelet function reduces significantly after heparin administration. Hemodilution and predominantly heparin are the causes of platelet dysfunction after cardiac surgery.