Background and Purpose-Emboli and proinflammatory mediators are suspected of generating cerebral edema after coronary surgery. In contrast to cardiopulmonary bypass (CPB), off-pump coronary artery bypass surgery (OPCAB) reduces microemboli count and proinflammatory mediator release but carries the risk of hemodynamic instability. A microaxial blood pump can augment cardiac output. Methods-Coronary bypasses were constructed in pigs with CPB and cardioplegia (nϭ9), OPCAB (nϭ9), or blood-pump support CAB (nϭ9). Nine animals underwent sham operation. Embolus count was monitored and regional cerebral blood flow was assessed with microspheres in 21 brain specimens per animal (nϭ189 per group). Interleukins 6 and 8 and tumor necrosis factor-␣ concentrations were determined. These variables were studied before, during, and for 4 hours after surgery. Finally, cerebral water content was determined. Results-During CPB and blood-pump CAB, a significant number of emboli were counted in contrast to OPCAB and controls (PϽ0.05). During CPB, regional cerebral blood flow was affected (32 of 189) and showed reactive hyperemia except in 10 specimens after aortic cross-clamp release. This impairment persisted in 20 specimens. During and after OPCAB, regional cerebral blood flow remained nearly unchanged but showed low flow during (58 of 189) and after (35 of 189) the blood-pump run. A significant increase in proinflammatory mediators was observed only in the CPB group. CPB and blood-pump CAB significantly increased cerebral water content (PϽ0.05). A strong correlation between embolic load and cerebral water content was observed in all groups. No correlation between proinflammatory mediator release and cerebral water content was detected. Conclusions-Emboli formation rather than inflammatory mediators are responsible for increased cerebral water content after conventional and assisted beating-heart myocardial revascularization. (Stroke. 2008;39:213-219.)