Low circulating von Willebrand factor levels increase the risk of bleeding after cardiac surgery. Patients with blood group O may be at greatest risk owing to lower baseline levels of von Willebrand factor compared with patients with other blood groups, and perioperative hemodilution during cardiac surgery may reduce von Willebrand factor to critical levels in these patients. This study tested the hypothesis that patients with blood group O are at increased risk for postoperative bleeding following cardiac surgery, and determined whether the blood group affected perioperative assessment of primary hemostasis. Using multivariate linear regression models that included preoperative and intraoperative covariates, the risk factors for postoperative bleeding were evaluated in 877 patients undergoing primary, nonemergent coronary artery bypass surgery at a university hospital. In a subset of these patients, we measured perioperative in-vitro bleeding times (PFA-100 analyzer) to determine whether there were measurable differences in primary hemostasis between patients with blood type O and those with other blood groups. Patients with blood group O did not have increased bleeding after cardiac surgery compared with patients with other blood types. In addition, while blood group O patients had laboratory evidence for abnormal primary hemostasis before surgery, there were no measurable differences in postoperative primary hemostasis in patients with different blood types. In conclusion, although we identified clinical and procedural factors that were independently associated with bleeding, blood group was not one of these factors.