Background Studies on selected patients undergoing off-pump versus on-pump coronary artery bypass surgery have produced inconsistent results, especially in patients with multiple coronary artery disease. This study compared the clinical results of on-pump and off-pump coronary bypass surgery in patients with triple-vessel disease.Methods A total of 300 consecutive isolated, multiple coronary artery bypass grafting (CABG) patients were assigned to the off-pump coronary artery bypass (OPCAB, n=150) or CABG with cardiopulmonary bypass (CCABG, n=150) groups. There were no significant differences regarding degree of angina, history of myocardial infarction or diabetes, and presence of left main coronary artery disease between the two groups. Ejection fraction in the OPCAB group before surgery was lower than in the CCABG group (P<0.01). In addition, more patients had a history of stroke and abnormal renal function preoperatively in the OPCAB group(P< 0.01). In OPCAB patients, single deep pericardial stay suture with a sling snared down was used to expose the target vessels, along with a stabilizer and a coronary shunt. A Medi-Stim Butterfly Flowmeter was used to measure blood flow through grafts in both groups.Results No OPCAB patient was converted to the CCABG group. The average numbers of distal anastomoses and the indexes of completeness of revascularization (ICR) were similar in both groups. Postoperative respiratory support time and the volumes of chest tube drainage and of blood transfusions were less in the OPCAB group than in the CCABG group (both P<0.01). The postoperative incidences of pulmonary dysfunction and renal insufficiency were lower in the OPCAB group than in the CCABG group (both P<0.05). There were no significant differences between the two groups in mortality and other causes of morbidity (periopetative myocardial infarction, stroke, atrial fibrillation). Conclusions OPCAB can be applied to patients with triple-vessel coronary artery disease and can achieve similar completeness of revascularization and similar early surgical results, with shorter respiratory support, reduced transfusion requirement, and fewer cases of pulmonary dysfunction and abnormal renal function.