Conventional bypass grafting using cardioplegic arrestcontinues to be associated with some complications that may negatean otherwise successful procedure. Interest in off-pump bypassgrafting (OPCABG) in the mid-1990s presented surgeons with theoption of revascularization without the potential complications ofextracorporeal support if CPB can be avoided; a reduction in perioperativemorbidity and mortality is anticipated.The aim of our study is to compare both techniques regardingmortality, morbidity, complications and brain injury in both groupsof patients with ischemic heart disease.Patients and methods: Eighty patients (pts) were subjected toCABGs, 40 with off pump (group I) and the other 40 pts with onpump (group II) techniques. Patients in both groups were matchingas regards age, sex, risk factors, and number of bypassed coronaries.Pre-operatively and postoperatively all patients were subjected toclinical examination, ECG, chest X-ray, trans echocardiography,routine laboratory tests and serum S100 B protein as well as NeuronSerum Enolase (NSE). Brain injury will be evaluated by usingGlasgow Coma Scale and the neuromediators.Results: Intra-operatively, group I pts had statisticallysignificant shorter operative time (3.6 ± 0.6 vs. 4.1± 0.7 hours ingroup II, p < 0.001), less intra-operative bleeding –of medical causes- with lower intra-operative use of blood products (55% of pts ingroup I vs. 100% of group II) & lower incidence of arrhythmias(25% vs. 60% of group II). Post-operatively, group I showedstatistically significant shorter stay in intensive care unit (2.8 ± 0.7vs. 3.8 ± 1.3 days in group II; p < 0.001), earlier extubation (9.4 ± 4vs 15.5 ± 11.6 hours in group II; p < 0.002), lower pulmonarycomplications as regard atelectasis, chest infection (5% vs 22.5% ingroup II; p < 0.02), lower cardiac complications as regard atrial fibrillation , low cardiac output & need for use of inotropic support(55% vs 82.5% in group II; p < .007), less hypothermic with lowerincidence of postoperative bleeding with less need for use of bloodproducts & reopening. Group I showed significantly less renal(22.5% vs 52.5% in group II; p < 0.05) and less hepatic impairmentthan in pts of group II (20% vs 55% in group II, p < 0.05). Nostatistically difference between both groups as regards cardiacischemia, cardiac arrest, ECG changes, trans-thoracicechocardiographic findings, hematemesis, and sternal woundinfection. Finally, group I showed lower incidence of neurologicaldeficits (whether reversible or permanent) (5% vs 27.5% in group II;p<0.006).Despite the latter, postoperative values of neuromediatorsS100B protein & NSE showed a significant increase in both groupscompared to preoperative serum level denoting some brain ischemia(as regard S100B protein, 60 vs 20 pg/ml preoperatively in group I;p < 0.05 and 100 vs 35 pg/ml preoperatively in group II; p < 0.05),(NSE, 22 vs 6 ug/L preoperatively in group I; p < 0.05 and 20 vs 7ug/L preoperatively in group II; p<0.05). However; there is nostatistically significant difference between both groups regarding thepercent of increase of both mediators postoperatively (1.88% ingroup I vs 1.7% in group II; P value: non significant).Conclusions: 1. In the view of S100B and NSE serum levelsin both groups, no significant difference between both groupsregarding cerebral ischemia 2. Off-pump Coronary artery bypassgrafting is effective with success rate comparable to On-pumpCABG. 3. Off-pump technique is safer in patients with preoperativebleeding disorders, renal/hepatic impairment, pulmonary disorders,or high risk for stroke e.g. calcific aortic roots. 4. Off-pumptechnique saves expenses due to fewer complications and lesspostoperative stay in intensive care unit.