The objective of the present study was to determine if a new procoagulant molecule, carbon monoxide releasing molecule (tricarbonyldichlororuthenium (II) dimer; CORM-2) would improve coagulation following cardiopulmonary bypass (CPB). Plasma was obtained from patients undergoing elective cardiac surgery requiring CPB. Whole blood was collected and anticoagulated with sodium citrate after induction of anesthesia and again after CPB and heparin neutralization with protamine. Blood samples were centrifuged for 15 min, with plasma collected and stored at -80°C prior to analysis. Samples were subsequently exposed to 0 or 100 μmol/l CORM-2, with coagulation activated with tissue factor. Data were collected with thrombelastography until clot strength stabilized. Patients underwent CPB for 133 ± 61 min (mean ± SD). The velocity of thrombus formation was significantly decreased (52%) by CPB, as was clot strength (53%). Addition of CORM-2 to plasma samples obtained after CPB significantly increased the velocity of clot formation (75%) and strength (52%) compared to matched unexposed samples. The lesion of plasmatic coagulation associated with CPB was significantly improved in vitro by addition of CORM-2. If preclinical assessments of efficacy and safety of CORM-2 are favorable, future clinical trials involving CORM-2 or other CORMs as a hemostatic intervention in the setting of CPB are justified.