Quantitative assessment of platelet dysfunction after cardiopulmonary bypass (CPB) and prediction of excessive microvascular bleeding remain elusive goals. We used a sensitive instrument capable of simultaneously measuring the force generated by platelets during plasma clot retraction and global clot strength. We hypothesized that CPB would significantly reduce these two variables. Platelet-rich plasma was obtained from eight patients undergoing aortocoronary revascularization prior to induction, after 90 min of CPB, and after protamine administration. Platelet force development was measured using a standardized technique that controlled for platelet number and permitted clot formation in the presence of heparin. Despite the presence of a measurable elastic modulus, platelet force development during bypass was abolished. Peak platelet force development after CPB was significantly lower than before CPB (5255 +/- 955 dynes vs 11,600 +/- 780 dynes, P = 0.01). The percent recovery (after/before bypass) of peak platelet force development inversely correlated with tube thoracostomy drainage during the first 24 h after placement (rs = -0.71, P = 0.048). This study demonstrates that CPB has dramatic effects on platelet force development. The correlation between the percent recovery of peak platelet force development and blood loss supports the clinical relevance of this measurement.