Background: Microwave energy is commonly used on the beating heart to create lesions for the surgical treatment of atrial fibrillation. However, lesion transmurality is likely to depend on several factors including tissue thickness and blood flow. This study was designed to determine the effect of cavitary blood flow on transmurality of acute atrial lesions with the FLEX 10 (Guidant Corporation, Santa Clara, Calif) microwave device. Methods: Six pigs underwent median sternotomy and were placed on cardiopulmonary bypass. Microwave lesions on the atrium were performed for 60 seconds at 65 Watts at 4 different levels of cardiac output by varying cardiopulmonary bypass flow rates. Cardiac output was measured with a pulmonary artery flow probe. Four additional lesions on 2 animals were done for 120 seconds at 65 Watts with 0.0 to 0.5 L/min cardiac output. The animals were sacrificed, and tissue was stained with 2,3,5-triphenyltetrazolium chloride and sectioned at 5-mm intervals. Lesion depth and width were determined from photomicrographs. Results: Sixty-second lesions were transmural in 90%, 65%, 54%, and 46% of atrial sections at cardiac output of 0.0 to 0.5 L/min, 0.6 to 1.9 L/min, 2.0 to 3.9 L/min, and 4.0 L/min or greater, respectively (P < .001). When ablations were performed for 120 seconds with a cardiac output of 0.0 to 0.5 L/min, 100% of lesions were transmural. Lesion width was also related to cardiac output, with the widest lesions produced when cardiac output was 0.0 to 0.5 L/min. Conclusions: Acute microwave ablation lesion depth and width are strongly dependent on the magnitude of cardiac output. Transmural lesions can be reliably produced on the porcine heart only while on cardiopulmonary bypass.