The protective effects of preprocedural esmolol on myocardial injury and hemodynamics have not, to date, been investigated in patients who were scheduled for cardiac surgeries under a cardiopulmonary bypass (CPB). A pilot randomized controlled trial was performed at The First Affiliated Hospital of Dalian Medical University (Dalian, China). Patients scheduled for elective open-heart surgeries under CBP were included, and were randomized to esmolol and control groups. For patients in the esmolol groups, intravenous esmolol (70 µg/kg/min) was administered at the time of incision until CPB was performed. For patients assigned to the control group, equal volumes of 0.9% saline were administered. Markers of myocardial injury and hemodynamic parameters were observed until 12 h post surgery. A total of 24 patients were included in the present study. No significant differences in hemodynamic parameters, including the central venous pressure and heart rate, were detected between patients in the two groups during the perioperative period or within the first 12 h post-surgery (P>0.05), except for the mean arterial pressure, which was higher in the esmolol group compared with the control group at 5 and 12 h post-surgery (P<0.05). However, the serum level of cardiac troponin I was higher in patients of the control group compared with those of the esmolol group during the preoperative period (P<0.05). Although creatinine kinase was significantly different at T2 between the two groups, its MB isoenzyme was not significantly different between the groups (P>0.05). In addition, administration of esmolol was not associated with an increased risk for severe complications and adverse events in these patients. In conclusion, preoperative esmolol may be an effective and safe measure of myocardial protection for patients who undergo elective cardiac surgeries under CBP.