In this study, we investigated whether cardioprotective properties of sevoflurane were expressed in patients with rheumatic heart disease undergoing heart valve surgery under cardiopulmonary bypass (CPB). Fifty patients with rheumatic heart disease undergoing heart valve surgery under CPB were randomly assigned to receive total anesthesia with sevoflurane or propofol during surgery. Except for this, anesthetic and surgical management was the same in all patients. The primary outcomes were postoperative high-sensitive cardiac troponin T (hs-cTnT) and creatine kinase-myocardial band (CK-MB) release. The secondary outcomes were hemodynamic events and short-term clinical outcomes (within 30 days after surgery). The plasma concentrations of hs-cTnT at 24-hour and CK-MB from 6-hour to 48-hour in the sevoflurane group were lower than those in the control group (the propofol group). After aortic unclamping, heartbeat recovery was faster and the rate of sinus rhythm was higher in the sevoflurane group than in the control group. Moreover, a lower proportion of pacemaker use and the need for intraoperative and postoperative inotropes were also found in the sevoflurane group. Nevertheless, there were no differences between the two groups regarding short-term clinical outcomes (durations of mechanical ventilation, intensive care unit stay, hospital stay, morbidity, and mortality rates). Sevoflurane administered during the entire anesthetic procedure had a myocardial protective effect with less evidence of myocardial damage in the first 48-hour postoperatively but short-term clinical outcomes were not significantly different when compared with the control group in patients with rheumatic heart disease undergoing heart valve surgery under CPB.