Background: Administration of Protamine sulfate for heparin neutralization after cardiopulmonary bypass may be associated with adverse reactions such as transient hypotension to cardiovascular collapse. Although catastrophic events are rare and occur only in 2.6% of cardiac surgeries, it is associated with adverse postoperative outcome. The aim of this study is to investigate whether bolus administration of CALCIUM GLUCONATE can minimize the adverse hemodynamic effects of protamine.Patients and Methods: This randomized clinical trial (RCT) prospective study was conducted between Feb. 2006 to Dec. 2008. The patients were randomly allocated into three groups including group A (42 patients) who received only protamine after weaning from cardiopulmonary, group B (44 patients) concomitantly treated with protamine sulfate and CALCIUM GLUCONATE, and group C (40 patients) receiving CALCIUM GLUCONATE 5 minutes before administration of protamine. Hemodynamic variables such as systolic and diastolic blood pressures, mean of arterial pressure, central venous pressure and heart rate were obtained 0, 2, 4, 6, 8 and 10 minutes after protamine administration from each group.Results: Systolic blood pressure in groups A (control) and C (CALCIUM administration before protamine) 0,2,4,6,8 and 10 minutes after protamine administration initially decreased and increased subsequently (P=0.228). Also no statistically significant difference was found in diastolic blood pressure (DBP), mean arterial pressure (MAP), central venous pressure (CVP), and heart rate (HR) in 0,2,4,6,8, and 10 minutes in any of the three groups. Conclusion: In our study, hemodynamic changes in 10 minutes after protamine administration for heparin neutralization in patients with good left ventricular systolic function after coronary artery bypass grafting surgery were mild, and prophylactic CALCIUM GLUCONATE administration concurrent with or before protamine injection was not recommended.