Haemostatic activation during cardiopulmonary bypass is associated with prothrombotic complications. Although it is not possible to detect and quantify haemostatic activation directly, platelet dysfunction, as measured with point‐of‐care‐assays, may be a useful surrogate. In this study, we assessed the association between cardiopulmonary bypass‐associated platelet dysfunction and adverse outcomes in 3010 cardiac surgical patients. Platelet dysfunction, as measured near the end of the rewarming phase of cardiopulmonary bypass, was calculated as the proportion of non‐functional platelets after activation with collagen. Logistic regression and multivariable analyses were applied to assess the relationship between platelet dysfunction and a composite of in‐hospital death; myocardial infarction; stroke; deep vein thrombosis or pulmonary embolism; and acute kidney injury (greater than a two‐fold increase in creatinine). The outcome occurred in 251 (8%) of 3010 patients. The median (
IQR[range]) percentage platelet dysfunction was less for those without the outcome as compared with those with the outcome; 14% (8–28% [1–99%]) vs. 19% (11–45% [2–98%]), p < 0.001. After risk adjustment, platelet dysfunction was independently associated with the composite outcome (p < 0.001), such that for each 1% increase in platelet dysfunction there was an approximately 1% increase in the composite outcome (OR 1.012; 95% CI1.006–1.018). This exploratory study suggests that cardiopulmonary bypass‐associated platelet dysfunction has prognostic value and may be a useful clinical measure of haemostatic activation in cardiac surgery.