Comparison between off-pump coronary bypass surgery ( OP-CABG )and conventional CABG ( C-CABG ) remains a controversial issue. OBJECTIVE To compare short and long term OP-CABG and C-CABG results in high-risk patients ( pts ), in absence of usual bias. METHODS A prospective observational study of 752 pts ( 252 pts with C-CABG and 500 with OP-CABG ) consecutively operated throughout 23 months by 4 surgeons largely experienced in both CABG modalities. For comparison of results, two groups ( Gr ) of pts were constituted - GrA, with 252 C-CABG pts, and GrB, with 252 OP-CABG pts - being the pts blindly matched for gender ( female sex - 51 pts ), age ( mean of 65 vs 64 yrs ), angiographic data ( 3 - VD ÷ left main - 92 % vs 90 % ), additive Euroscore ( mean of 4.6 vs 4.6 ), prior myocardial infarction ( 58 % vs 59 % ), history of diabetes ( 48 % vs 49 % ) or hypertension ( 83 % vs 83 % ). Other clinical data ( GrA vs GrB ): left ventricular dysfunction - 39 % vs 34 % ( NS ); logistic Euroscore - mean of 5.4 % vs 5.9 % ( NS ). Surgical results, in-hospital clinical evolution, in-hospital costs ( intra-operative and major post-operative costs ), and short-term ( mean of 50 days ) and long-term ( mean of 5 years ) follow-up were object of evaluation. Results ( GrA vs GrB ): 1 ) Nr of bypasses ÷ pt 2.9 vs 2.4 ( p < 0.01 ); nr of arterial conduits ÷ pt 1.2 vs 1.2; complete revascularization 60 % vs 60 %; surgical total time 155 ± 49 vs 136 ± 42 min ( p < 0.001 ); surgical total time in pts with 3 bypasses 157 ± 41 vs 156 ± 37 min ( NS ). 2 ) In-hospital post-operative evolution: inotropic support ( IS ) 46 % vs 29 % ( p < 0.001 ); heavy IS 14 % vs 6 % ( p < 0.025 ) ; uncomplicated post-operative course 18 % vs 26 % ( p < 0.025 ); significant CV events ( excluding atrial tachyarrhythmias ) 33 % vs 20 % ( p < 0.01 ); infection 22 % vs 14 % ( p < 0.05 ); severe complications 22 % vs 9.5 % ( p < 0.001 ); mean intensive care length of stay 4 vs 3 days ( p < 0.01 ); surgery-to-discharge length of stay 11.3 vs 9.8 days ( p ⋝ 0.05 ); in-hospital mortality ( HM ) 4.4 % vs 2.0 % ( NS ); HM + disabling chronic morbidity 7.5 % vs 3.2 % ( p < 0.05 ) . 3 ) In-hospital costs: intra-operative - superposable; post-operative - excess of about 900 euro ÷ pt in GrA. 4 ) Short-term follow-up: asymptomatic pts - 75 % vs 85 % ( p < 0.025 ); post-discharge complications - 8.3 % vs 7.7 % ( NS ); probability of being alive and asymptomatic + 17 % in GrB ( p < 0.01 ); mortality 0 % vs 0 %. 5 ) Long-term-follow-up ( 87 % vs 90 % pts ), at 5 years: pts alive with no clinical evidence of active coronary artery disease 72 % vs 75 % ( NS ); significant ÷ severe cardiac events of coronary origin 18.8 % vs 9.3 % ( p < 0.025 ); elective PTCA 4.8 % vs 2.3 % ( NS ); all-cause mortality 11.8 % vs 11.9 %; coronary mortality 6.9 % vs 4.4 % ( NS ). CONCLUSIONS In experienced hands and before high-risk pts, OP-CABG offers lesser post-operative risks than C-CABG, with clear and positive consequences on in-hospital costs and short-term follow-up. During long-term follow-up, the revascularization benefits obtained by OP-CABG are not inferior to those conferred by C-CABG, and a significant reduction of the incidence of severe cardiac events can even be seen in a particular subset of pts.