Protamine is used after cardiopulmonary bypass was stopped in order to reverse the anticoagulant effects of heparin administered during open-heart operations. Adverse hemodynamic responses to protamine are common, ranging from minor perturbations to cardiovascular collapse. The aim of the present study was to investigate whether a prostacyclin is effective in the treatment of protamine-mediated acute pulmonary hypertension and right ventricular failure in the perioperative period of isolated coronary artery bypass grafting (CABG) operations. In sixty-eight (1.78%) of 3800 patients who underwent isolated CABG, acute pulmonary hypertension and right ventricular failure developed during or following the protamine infusion. These 68 patients were included in the study and were randomized into two groups. Thirty-eight of the patients received prostaglandin I(2) (PGI(2)), norepinephrine and dopamine (PGI(2) group), whereas 30 patients received nitroglycerin, norepinephrine and dopamine (control group). Hemodynamic data were recorded before and after the above drug combinations. The mean value of left ventricle ejection fraction significantly increased (p < 0.05) and mean values of central venous pressure, pulmonary artery systolic and diastolic pressure, pulmonary capillary wedge pressure and pulmonary vascular resistance significantly decreased (p < 0.05) in the PGI(2) group. The mean value of pulmonary capillary wedge pressure significantly decreased (p < 0.05) and the mean value of central venous pressure significantly increased (p < 0.05) in the control group. In conclusion, prostacyclin (PGI(2)) is effective in the treatment of protamine-mediated acute pulmonary hypertension and right ventricular failure in the perioperative period in isolated CABG operations. This finding may be an important contribution to the treatment of severe protamine complications during open-heart operations.