To determine whether patients with critical left main stem (LMS) coronary artery disease can undergo off-pump coronary artery bypass (OPCAB) surgery safely and successfully. From May 1996 to March 2000 data for patients with critical (> or =50%) LMS stenosis who underwent conventional coronary artery bypass surgery with cardiopulmonary bypass (CCAB) or without (OPCAB) were collected prospectively using the Patient Analysis & Tracking System. A reusable pressure stabilizer, intra-coronary shunts and a single posterior pericardial stitch exposure technique were used in all OPCAB cases. Non-randomized, retrospective data analysis included demographic and preoperative risk factors, operative details, clinical outcome and early follow-up. During the study period 387 patients with LMS stenosis underwent surgery (OPCAB n=75, CCAB n=312). Groups were similar in terms of preoperative and intraoperative variables although CCAB patients received significantly more grafts per patient (3.1+/-0.73 vs. 2.6+/-0.76, P< or =0.001). Mortality was similar in both groups (OPCAB 1.3% vs. CCAB 2.6%). OPCAB patients when compared to CCAB patients had a lower requirement for postoperative inotropes (12.0% vs. 38.1%, P=0.0001), temporary postoperative pacing (2.7% vs. 10.1%, P=0.02), and blood product transfusion (6.7% vs. 31.4%, P<0.0001), a lower incidence of postoperative chest infection (0% vs. 6.7%, P=0.02) and a slightly reduced postoperative length of stay (7.9+/-5.46 vs. 8.3+/-5.11 days, P=0.01). At 24 months follow-up, CCAB and OPCAB actuarial survival was 94.1+/-1.7% and 97.7+/-2.3%, respectively. OPCAB surgery is safe and effective in patients with critical LMS disease.