Abstract: Objective To explore clinical outcomes of nitroglycerin perfusion via the aortic root before heart re-beating for patients undergoing heart valve replacement. Methods A total of 254 patients with valvular heart diseases underwent heart valve replacement in Beijing Anzhen Hospital from January 2008 to December 2011. According to whether or not they received nitroglycerin perfusion via the aortic root before heart re-beating during cardiopulmonary bypass (CPB), all the 254 patients were randomly divided into two groups, the nitroglycerin group and the control group. There were 134 patients in the nitroglycerin group including 57 males and 77 females with their average age of 58.47±12.34 years. They received aortic root perfusion of 5 mg nitroglycerin diluted into 20 ml after full de-airing of the heart, and repeated aspiration was performed 8 to 10 times before heart re-beating during CPB. Aortic cross-clamp was released after the heart showed signs of automatic re-beating, and the aortic root was squeezed in high frequency by hand to make sure that the aorta was squeezed to close each time. In the control group, there were 120 patients including 64 males and 56 females with their average age of 61.85±11.97 years. Patients in the control group received routine procedures of CPB except nitroglycerin perfusion before heart re-beating. Automatic heart re-beating rate, CPB supporting time after heart re-beating, postoperative usage of inotropic drugs, mechanical ventilation time, perioperative morbidity and length of hospital stay were compared between the 2 groups, and patients were followed up and further evaluated. Results There was no in-hospital death. CPB supporting time after heart re-beating(12.32±9.76 min vs. 23.43±10.33 min, t=-1.233, P=0.000), dopamine usage[3.45±2.33 μg/ (kg?min) vs. 5.67±3.12 μg/ (kg?min) , t=-0.943 , P=0.034] and epinephrine usage [0.026±0.013 μg/ (kg?min) vs. 0.056±0.021 μg/ (kg?min) , t=-0.822 , P=0.027] of the nitroglycerin group were significantly shorter or lower than those of the control group. Automatic heart re-beating rate of the nitroglycerin group was significantly higher than that of the control group [97.01% vs. 66.67 % , χ 2 =-2.115 , P=0.000]. A total of 121 patients in the nitroglycerin group were followed up for 2-36 months, and 13 patients were lost during follow-up. There was no death during follow-up. Conclusion For patients undergoing heart valve replacement, some myocardial protection strategies including nitroglycerin perfusion via the aortic root before heart re-beating, use of norepinephrine, and aortic root squeezing in high frequency by hand can significantly increase the automatic heart re-beating rate, shorten the CPB supporting time after heart re-beating, and improve postoperative clinical outcomes.