OBJECTIVE The Hepcon Heparin Management System (HMS) facilitates administration of higher heparin and lower protamine doses, which may affect bleeding potential due to heparin rebound. The present study evaluated heparin rebound in patients for whom the Hepcon HMS was used to determine whether point-of-care tests detect residual heparin and residual heparin is associated with postoperative blood loss. METHODS Prospective study. METHODS Tertiary care center affiliated with a university hospital. METHODS Adults undergoing elective cardiac surgery requiring cardiopulmonary bypass. METHODS In blood samples obtained at baseline, at 2 minutes, and at 1, 2, 4, 6, and 24 hours after heparin neutralization, heparin concentrations were measured using an automated chromogenic assay. Activated coagulation time (ACT), activated partial thromboplastin time (APTT), and thromboelastometry 2 hours after heparin neutralization also were examined in the last 22 study patients enrolled. RESULTS All 31 patients had measurable heparin levels 2 hours after protamine administration; 22 patients exhibited a primary failure to reverse heparin after protamine administration, and 9 patients had measureable heparin levels 2 hours after complete heparin reversal (ie, heparin rebound). The thromboelastometric variable, INTEM-CT:HEPTEM-CT ratio, correlated with heparin concentration (r=0.72), but ACT (r=-0.12), APTT (r=0.36), and whole blood heparin concentration, determined using the Hepcon HMS, did not. Peak heparin concentration (0.18±0.07 U/mL) at 4 hours was not correlated with mediastinal blood loss. CONCLUSIONS Circulating heparin detected by the chromogenic assay was too low to be clinically significant based on postoperative bleeding, although all 31 patients had residual heparin or heparin rebound at 2 hours after protamine administration with use of the Hepcon HMS.