The use of dosing assays to calculate heparin and protamine dose requirements during cardiac surgery has been shown to significantly improve overall postoperative patient outcome. When patients are managed with an individualized dosing system, intraoperative and postoperative transfusion requirements and bleeding are reduced. The Hemochron RxDx system is widely used as a complement to traditional activated clotting time testing to optimize anticoagulation management. The system consists of the heparin response test, the protamine response test, and the protamine dose assay. All are modifications of the activated clotting time using either Celite (Celite Corporation, Santa Barbara, CA) or kaolin as the activator. Dosing is calculated manually using earlier version Hemochron instruments (model 801) or automatically with the Hemochron 8000 or with the early versions of the Hemochron Response and the personal digital assistant (PDA) RxDx calculator. Missing from available user options is an automated RxDx system for the Response. A study was conducted at four clinical sites to compare recently developed Response RxDx software, which eliminates the need for the PDA RxDx calculator, to the existing Hemochron 8000 RxDx and to the Response-PDA RxDx systems. Similar to the current system, the operator inputs the patient's height, weight, and gender, and the software automatically calculates the blood volume. Using the clotting times determined on the Response, bolus heparin and protamine doses and any additional heparin and protamine requirements are calculated automatically. Data were collected from 76 patients, of which, 64 patients were on pump, 11 patients were off pump, and 1 patient was converted from off to on pump. The Response estimated blood volume calculations showed a correlation coefficient of 0.989 when compared with available systems. A good correlation was also observed for the bolus heparin (r = 0.925) and protamine doses (r = 0.900) with equivalence confirmed by a paired student's t test. These data confirm that the Response RxDx system yields results that are identical (P > 0.05) to those obtained using the Hemochron 8000 RxDx or Response-PDA RxDx calculator. The Response RxDx also offers expanded user options related to blood volume limits, expanded clotting time ranges for presetting default values, and flexibility in test sequence. Case records can be printed or downloaded to a PC via the HRDM data management program. The Hemochron Response RxDx represents a complete anticoagulation management system for the cardiac surgical patient.