Objective To evaluate the outcome and explore the mechanism of coronary vein bypass grafting (CVBG) performed by anastomosing the right internal mammary artery with the middle cardiac vein via off-pump surgery. Methods Twelve Chinese experimental miniswines (either male or female, age from 7 to 10 months, body weight 40±5 kg) with severely diffuse stenosis in the right coronary artery were randomly divided into control group and experiment group with 6 miniswines in each group, using a random number table method. CVBG was performed in the experiment group and sham surgery was performed in the control group. To assess cardiac function, graft flow, graft patency and micro-circulation reperfusion of ischemia myocardium, following measurements were conducted. Eight weeks after right coronary endarterectomy, transthoracic echocardiography was performed for both groups. Coronary angiography, graft flow and echocardiography were performed or measured 6 hours and 3 months after CVBG or sham surgery. Measurement of myocardial blood flow with non-radioactive colored microspheres was also conducted 3 months after surgery for two groups. Results There was no statistical difference in cardiac function 8 weeks after right coronary endarterectomy between the two groups. There were significant improvements in cardiac systolic and diastolic function (ejection fraction 3 months after operation: 52%±6% vs. 44%±5%, t=-2.500, P=0.031) in the experiment group after CVBG compared with the control group. Graft flow of the experiment group 6 hours and 3 months after CVBG were 44.50±5.86 ml/min and 43.33±5.01ml/min respectively (P=0.718), and pulsatility index (PI) was 0.73±0.14 and 0.80±0.14 respectively(P=0.858). Internal mammary artery grafts and the anastomoses were all patent without stenosis, documented by coronary artery angiography for the experiment group 6 hours and 3 months after CVBG. Myocardial flow in all aspects especially in the subendocardial layer, estimated by non-radioactive colored microsphere injection, was significantly higher in the experiment group after CVBG than that of the control group, transmural flow was 0.33±0.05ml/(g • min) vs. 0.19±0.03 ml/(g • min) (P<0.05). Conclusion Ischemic conditions of the myocardium can be relieved by CVBG using internal mammary artery in a short-term to medium-term period. The mechanism may be due to improvement of the myocardial micro-circulation.